Critical Care Nursing Monitoring and Treatment for Advanced Nursing Practice ( PDFDrive - Copy

CONTENTS
Cover
Title page
Copyright page
Contributors
Critical Care Nursing: Monitoring and
Treatment for Advanced Nursing Practice
Introduction
Chapter 1: Philosophy and treatment in US
critical care units
US critical care units
Organization of critical care delivery
Monitoring and surveillance in critical
care
Surveillance
Nursing certification and competency in
critical care units
US national critical care organizations
Acute care advanced practice nursing
Clinical nurse specialists
Acute care nurse practitioners
Critical care and ACNP outcomes
research
Evolution of families in the critical care
unit
2
Progression and development of rapid
response teams
References
Chapter 2: Vital measurements and shock
syndromes in critically ill adults
Monitoring basic vital signs
Respiratory monitoring
Shock conditions in critically ill adults
Other infectious complications in
critically ill adults
Monitoring during transport
Conclusion
References
Chapter 3: Monitoring for respiratory
dysfunction
Acid-base disturbances & anion gap
Metabolic acidosis
Oxygenation
Capnography
Modes of mechanical ventilation
Monitoring for complications during
mechanical ventilation
Weaning from mechanical ventilation
Sleep-disordered breathing in the critical
care unit
Conclusions
References
3
Chapter 4: Electrocardiographic monitoring
for cardiovascular dysfunction
Physiologic guidelines
Goals of monitoring
Acute coronary syndromes
Cardiac arrhythmias
Acute heart failure
Electrolyte abnormalities
Critical illnesses
Drug overdose
Unnecessary arrhythmia monitoring and
underutilization of ischemia and
QT-interval monitoring
References
Chapter 5: Hemodynamic monitoring in
critical care
Hemodynamic monitoring overview
Hemodynamic monitoring systems
Hemodynamic monitoring guidelines
and outcomes
References
Chapter 6: Monitoring for neurologic
dysfunction
Physiological guidelines
Rapid assessment of neurologic
dysfunction in intensive care unit
patients
Intracranial pressure monitoring
4
Measuring brain temperature
Brain tissue O2 monitoring
Microdialysis
Electrophysiological monitoring
The BiSpectral index monitoring
Transcranial Doppler ultrasonograpy
Shunts
Neuromuscular transmission
Management of cervical stabilization
devices
Research-based neurologic protocols
References
Chapter 7: Monitoring for renal dysfunction
Acute kidney injury
Physiological guidelines
Renal replacement therapy
References
Chapter 8: Monitoring for blood glucose
dysfunction in the intensive care unit
Diabetes management in the ICU
Conclusion
References
Chapter 9: Monitoring for hepaticand GI
dysfunction
Physiologic guidelines
Monitoring elements: nasogastric
decompression
5
Endoscopic procedures
Monitoring elements: gastric tonometry
and capnometry
Radiographic diagnostics
Ultrasonography
Treatment of abdominal compartment
syndrome
Diagnostics for liver function
Liver support devices
ICP monitoring in acute liver failure
Nutritional assessment and treatment
Critical monitoring in acute pancreatitis
Summary
References
Chapter 10: Traumatic injuries: Special
considerations
Primary, secondary, and tertiary surveys
Fluid resuscitation
Intracompartmental monitoring
Complications
Thoracic injury management
Abdominal trauma
Musculoskeletal injuries and
management
Burns
Summary
References
6
Chapter 11: Oncologic emergencies in
critical care
Evolution of oncology critical
management
Stem cell transplant
Hematologic complications
Management of electrolyte imbalances
Acute kidney injury
Structural emergencies
References
Chapter 12: End-of-life concerns
Introduction
Assessment and communication issues
Family presence
Advanced directives
Delivering bad news
Palliative care in the ICU
Brain death
References
Chapter 13: Monitoring for overdoses
Introduction
Indexing of drug and toxins seen in
overdoses
Common toxidromes and treatments for
poisoning conditions
Anion and non-anion gap acidosis and
osmolar anion gap
7
References
Index
End User License Agreement
List of Tables
Critical Care Nursing
Table 1 Titling of guidelines within the
National Clearinghouse Guidelines Index
(2012).
Chapter 01
Table 1.1 Family support in the ICU.
Chapter 02
Table 2.1 Recommendations for
measuring temperature.
Table 2.2 Beneficial effects of
hypothermia.
Table 2.3 Clinical signs associated with
malignant hyperthermia.
Table 2.4 Published class I ECG
monitoring guidelines for heart rate and
rhythm changes in adults.
Table 2.5 Cuff sizes for appropriate BP
measurement in adults.
Table 2.6 Abnormal respiratory patterns
commonly seen in ICU patients.
Table 2.7 Assessment findings in sepsis.
8
Table 2.8 Risk factors for sepsis.
Table 2.9 Sepsis diagnostic criteria.
Chapter 03
Table 3.1 Causes of metabolic acidosis.
Table 3.2 Parameters for liberating
(weaning) from mechanical ventilation.
Table 3.3 WEANS NOW checklist to
assess failure to wean 48–72 h after
resolution of underlying condition
causing respiratory failure.
Table 3.4 American Association of
Respiratory Care criteria for noninvasive
positive pressure ventilation for
exacerbation of COPD.
Table 3.5 Treatment options for
sleep-disordered breathing in the critical
care unit(assuming data from prior
sleep study is not available).
Chapter 04
Table 4.1 Biomarkers used for diagnosis
of acute MI.
Table 4.2 Monitoring recommendations,
vessels, and selected leads.
Table 4.3 ECG monitoring arrhythmia
classifications.
Chapter 05
9
Table 5.1 Terms associated with
hemodynamic monitoring.
Table 5.2 Principles of hemodynamic
monitoring.
Table 5.3 Factors affecting SvO2. Svo2 is
a sensitive indicator of oxygen supply/
demand balance, If Svo2 decreases to
less than 50%, the patient should be
rapidly assessed for the cause of an
increased oxygen demand, or decrease in
supply. Anemia, hypoxemia, and
decreased CO may result in markedly
reduced oxygen delivery. In the presence
of the high metabolic demands imposed
by critical illness, a reduction in O2
delivery or further increase in O2
demand can produce profound
instability in the patient. Changes in
Svo2 often precede overt changes
reflective of physiologic instability.
Chapter 06
Table 6.1 Intracranial pressure
monitoring options.
Table 6.2 Differences in brain and body
temperatures.
Table 6.3 BIS values and corresponding
levels of sedation
Chapter 07
10
Table 7.1 AKIN Classification/Staging
System for Acute Kidney Injury.
Table 7.2 Etiologies of prerenal injury.
Table 7.3 Common causes of intrarenal
failure.
Table 7.4 Drugs causing acute interstitial
nephritis.
Table 7.5 Physical assessment findings in
prerenal failure.
Table 7.6 Differential laboratory
diagnosis of renal dysfunction.
Table 7.7 Electrolyte imbalances related
to AKI.
Table 7.8 Urinary findings in acute
kidney injury.
Table 7.9 Diagnostic imaging in acute
kidney injury.
Table 7.10 Modalities of CRRT.
Table 7.11 Comparison of renal
replacement therapies.
Chapter 08
Table 8.1 Management options for
insulin coverage of fingerstick glucose
(FSG) testing before meals and at
bedtime (Hospital of Central
Connecticut).
11
Table 8.2 Hypoglycemia protocol:
options based on mental status.
Chapter 09
Table 9.1 Clinical grades of hepatic
encephalopathy.
Table 9.2 Indications for endoscopic and
angiographic therapy in acute upper and
lower GI bleeding.
Table 9.3 Monitoring priorities for intraand postendoscopic therapy.
Table 9.4 FAST guideline summary for
abdominal ultrasonography.
Table 9.5 Management strategies for
ascites.
Chapter 10
Table 10.1 Primary and secondary survey
of the trauma patient.
Table 10.2 Tertiary survey of the trauma
patient.
Table 10.3 Massive transfusion product
(MTP) shipment table.
Table 10.4 Differential diagnosis and
management of gastroparesis, small
bowel ileus, and colonic ileus.
Table 10.5 Organ dysfunction caused by
increased intracompartmental pressure.
12
Table 10.6 Prophylactic antibiotic use in
open fractures.
Table 10.7 Extremity nerve assessment.
Chapter 11
Table 11.1 Laboratory and clinical
findings in tumor lysis syndrome.
Table 11.2 Signs and symptoms of tumor
lysis syndrome.
Table 11.3 Traditional oncologic
emergencies.
Chapter 12
Table 12.1 Strategies for improving
end-of-life communication in the
intensive care units.
Table 12.2 Domains of quality palliative
care and overview of clinical practice
guidelines.
Table 12.3 Core competencies in
palliative care for pulmonary and critical
care clinicians recommended by theAd
Hoc ATS End-of-Life Care Task Force.
Table 12.4 Checklist for declaring brain
death, consistent with these guidelines.
Chapter 13
Table 13.1 Methemoglobin levels and
associated symptoms.
13
Table 13.2 Drug-induced hyperthermia
syndromes.
Table 13.3 MAO/MAOI drug
interactions.
Table 13.4 MAO/MAOI food
interactions.
Table 13.5 Overdose of beta blockers:
effects and treatment.
Table 13.6 Drugs that cause prolonged
QT interval (not all inclusive).
Table 13.7 Common drug or toxin
overdose and antidotes.
List of Illustrations
Chapter 01
Figure 1.1 Knowledge transformation
processes.
Chapter 02
Figure 2.1 Anaphylaxis algorithm.
Chapter 03
Figure 3.1 Diagnostic algorithm for
metabolic acidosis.
Figure 3.2 Diagnostic algorithm for
metabolic alkalosis.
Figure 3.3 Diagnostic algorithm for
respiratory acidosis.
14
Figure 3.4 Diagnostic algorithm for
respiratory alkalosis.
Figure 3.5 Phases of the capnogram.
Figure 3.6 CPAP, PS, and AC patterns.
Figure 3.7 Auto-PEEP effect.
Figure 3.8 Common landmarks and
structures of the chest radiograph. (a)
Projection and the lateral. (b) Projection.
Chapter 04
Figure 4.1 Posterior V7–V9 placement.
Figure 4.2 Electrode placement for right
ventricular and posterior infarction
detection.
Chapter 05
Figure 5.1 Waveforms during insertion of
pulmonary artery catheters.
Figure 5.2 Mechanisms of SVV during
positive pressure ventilation.
Figure 5.3 SVV and fluid responsiveness.
Figure 5.4 Physiologic optimization
program using Stroke Volume Variation
(SVV) and Stroke Index (SI).
Chapter 06
Figure 6.1 Cerebral autoregulation. The
Major physiological system involved in
the complex regulation of blood
pressure. Dotted lines represent local
15
autoregulation, solid lines represents
neural influences, and dashed lines
represents neuroendocrine influence.
SNS, sympathetic nervous system.
Figure 6.2 Glasgow Coma Scale and
application.
Figure 6.3 National Institute of Health
Stroke Scale (NIHSS).
Figure 6.4 Two sections of BRAIN card.
Figure 6.5 The image on the left shows 4
windows of transcranial Doppler
insonation. Clockwise these are orbital,
temporal, submandifular, and foraminal.
The image on the right shows the 3
aspects of the temporal window: 1)
middle; 2)posterior; and 3)anterior.
Adapted with permission from Wiegand,
D.J.L., and the American Association of
Critical-Care Nurses (AACN) (2011).
Figure 6.6 Cervical spine stabilization
from AANA (2007). Cervical Spine
Surgery. A Guide to Preoperative Patient
Care. Used with permission from AANA.
Chapter 07
Figure 7.1 RIFLE classification/staging
system for AKI.
Chapter 08
16
Figure 8.1 Potential pathophysiological
associations between sleep disorders and
diabetes.
Figure 8.2 Critical care insulin infusion
protocol (Hospital of Central
Connecticut).
Figure 8.3 Subcutaneous insulin
correction scales for patients on
tube-feeding diets.
Chapter 09
Figure 9.1 Gastrointestinal tract.
Figure 9.2 Ligament of Treitz.
Figure 9.3 Gastric tonometry.
Figure 9.4 Patient positioning for
intraabdominal pressure measurement.
Chapter 10
Figure 10.1 Traumatic brain injury
management algorithm, Carle
Foundation Hospital. *Unless ICP rises
>20. **Stop if PbtO2 falls <20.
***Vasopressors to bring CPP > 60.
Inotropes to increase CI. ****If CPP <
60, consider inotropes. If CPP < 60,
consider vasopressors. NOTE: This
protocol provides for all factors that
should be considered.
Figure 10.2 Stages of damage control
surgery.
17
Figure 10.3 Burn evaluation and Lund/
Browder chart.
Chapter 11
Figure 11.1 Suggested adjustments to the
empirical antibiotic regimen after 3–5
days treatment.
Figure 11.2 Electrical alternans in
malignant cardiac tamponade.
Twelve-lead electrocardiogram shows
electrical alternans. Note the alternating
amplitude and vector of the P waves,
QRS complexes, and T waves.
Figure 11.3 Carotid blow-out syndrome
algorithm.
18
Critical Care Nursing
Monitoring and Treatment for
Advanced Nursing Practice
EDITED BY
Kathy J. Booker, PhD, RN, CNE
Professor, School of Nursing Millikin University
Decatur, Illinois, USA
19
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Library of Congress Cataloging-in-Publication
Data
Critical care nursing (Booker)
Critical care nursing : monitoring and
treatment for advanced nursing practice /
[edited by] Kathy J. Booker.
p. ; cm.
Includes bibliographical references and
index.
ISBN 978-0-470-95856-8 (pbk.)I.
Booker, Kathy J., editor. II. Title.
[DNLM: 1. Critical
Care–methods–Handbooks. 2. Nursing
Care–methods–Handbooks. WY 49]
RC86.8
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2014030769
A catalogue record for this book is available
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Cover image: © iStockphoto / agentry / File #
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23
Contributors
Jennifer Abraham, RN, BS
Staff Nurse Medical/Oncology
Advocate BroMenn Medical Center
Normal, IL., USA
Laura Kierol Andrews, PhD, APRN,
ACNP-BC
Associate Professor
Yale School of Nursing
Orange, CT., USA and Senior ACNP,
Department of Critical
Care Medicine
Hospital of Central Connecticut, New Britain,
CT., USA
Lisa M. Barbarotta, RN, MSN, AOCNS,
APRN-BC
Nurse
Practitioner,
Hematology-Oncology
Service
Smilow Cancer Hospital at Yale-New Haven
New Haven, CT., USA
Catherine L. Bond, MS, MSED, ACNP-BC,
TNS
Nurse Practitioner
Critical Care Team
Carle Foundation Hospital
Urbana, IL., USA
24
Kathy J. Booker, PhD, RN, CNE
Professor, School of Nursing,
Millikin University
Decatur, IL., USA
Dawn Cooper, MS, RN, CCRN, CCNS
Service Line Educator
Medical Intensive Care Unit
Yale New Haven Hospital York Street Campus
New Haven, CT., USA
Linda M. Dalessio MSN, ACNP-BC, CCRN
Assistant
Professor,
Nursing
Western
Connecticut State University
Danbury, CT., USA
Eleanor R. Fitzpatrick, RN, MSN, CCRN
Clinical Nurse Specialist for Surgical Intensive
Care & Intermediate Care Units
Thomas Jefferson University Hospital
Philadelphia, PA., USA
Carey Heck, MS, MSN, ACNP-BC, CCRN,
CNRN
Instructor
Jefferson School of Nursing
Philadelphia, PA, USA
Janice L. Hinkle, RN, PhD, CNRN
Nurse Author and Editor
Washington, DC, USA
Alexander P. Johnson, MSN, RN, CCNS,
ACNP-BC, CCRN
Critical Care Clinical Nurse Specialist
25
Cadence Health, Central DuPage Hospital
Winfield, IL., USA
Mary Beth Voights, MS, RN, CNS
Trauma Services Coordinator
Carle Foundation Hospital
Urbana, IL., USA
Catherine Winkler, PhD, MPH, RN
Professor
Fairfield University
Fairfield, CT., USA
26
Critical Care Nursing:
Monitoring and Treatment for
Advanced Nursing Practice
Kathy J. Booker
Introduction
The many contributions to patient care and
safety made by critical care nurses have been
substantial since the inception of critical care
units. As advanced nursing practice has
expanded into high-risk and complex
environments, the role of careful monitoring
and surveillance to care management has
become exponentially important to patient
safety. However, wide variation in practice and
outcomes across the nations’ critical care units
continues. Monitoring the condition and
progress of critically ill adults remains vital to
good patient outcomes but many treatment and
monitoring protocols are still grounded in
descriptive and observational studies and
expert practitioner experience. Although a
substantial number of evidence-based protocols
have been refined over the past decade, many
monitoring practices have not been sufficiently
studied. This book is designed to guide critical
care nurses and advanced practitioners by
examining guidelines and evidence-based
27
treatment recommendations associated with
assessment and monitoring of patient
conditions commonly treated in critical care
units. It embraces recent advancements in the
concept of surveillance as a mainstay of clinical
quality.
There is considerable variation in levels of
evidence and practice guidelines. Within the
National Clearinghouse Guidelines alone, vastly
varied titles of guidelines can be found among
the over 2500 guidelines housed in 2012 (Table
1). These title variations, while selected by
authors and organizations, reflect the difficulty
clinicians face in locating clinical practice
guidelines and standards of care. As sources of
published guidelines expand, clinicians may
find multiple care practice patterns unique to
customary practices by country, region, or
clinical organization, further compounding the
difficulty enacting practice changes.
Table 1 Titling of guidelines within the
National Clearinghouse Guidelines Index
(2012).
Medical guidelines Consensus
statements
Clinical practice
guidelines
Practice parameters
Guidelines of care
Guidelines for
monitoring and
management
28
Medical guidelines Consensus
statements
Guidelines for practice Assessment guidelines
Evidence reports
Evidence-based
guidelines
Clinical guidelines
Clinical policy: critical
issues
Medical guidelines for Quality indicators
clinical practice
Evidence-based
interventions
Standards of medical
care
Medical position
statements
Practice advisories
Evidence-based
patient safety
advisories
Evidence review and
treatment
recommendations
Best practice
Care of patient
guidelines and policies guidelines
Guidelines for
management
Clinical expert
consensus
Recommendations for Recommendations for
standardization and
delivery of care and
interpretation
ensuring access
Despite titling confusion, clinicians have more
data to guide practice than in prior decades.
Within this text, chapter editors have sought to
examine the evidence base of practices in
critical care monitoring and care delivery in
29
critical care systems. While no single evidence
system has been applied, strong evidence is
acknowledged in systematic reviews of
phenomena amenable to randomized controlled
studies. Moderate levels of evidence advocated
by most sources are supported in published
guidelines from well-designed qualitative and
quantitative studies. However, many of the
practices currently used to monitor critically ill
patients remain at the level of weak evidence or
expert opinion. Protocols, even those based on
strong evidence, do not always apply to every
unique patient condition. Patient choice and
philosophy should guide implementation of any
monitoring and treatment practice. In addition,
in many practices that are not widespread or
targeted by review organizations due to high
risk for poor outcomes, weak evidence
continues because of a lack of practice
guidelines. Study funding remains a barrier to
advancing best practice for the nation’s
critically ill. As systems improve for organizing
and applying research findings, improvements
in patient outcomes will continue to be
advanced. Always, critical care nursing practice
remains grounded in human ethics and respect
for individualized care.
30
Chapter 1
Philosophy and treatment in
US critical care units
Kathy J. Booker
School of Nursing,
Decatur, IL., USA
Millikin
University,
In this chapter, the evolution of critical care
practice and advanced nursing roles are
explored. An examination of factors that
contribute to safe monitoring and treatment in
critical care units includes certification
processes and national support for critical care
nursing practice, perspectives on patient and
family-focused care, and the evolution of rapid
response team (RRT) roles in hospital settings.
US critical care units
Critical care units were formally developed in
the United States in the years following World
War II. Common elements driving the origin of
critical care units remain important even today,
including close patient monitoring, application
of
sophisticated
equipment,
and
surveillance-based interventions to prevent
clinical deterioration or health complications.
Today’s critical care units are often diverse,
specialized areas of care for patients at high risk
31
or those undergoing critical health events
requiring nursing attention. The critical care
team is generally quite complex, including
medical management increasingly supported by
intensivists, residents, acute care nurse
practitioners (ACNPs), clinical nurse specialists
(CNSs), and other nursing personnel.
Additional
vital
practitioners
include
respiratory therapists, dietitians, pharmacists,
social workers, and physical/occupational
therapists. Over the last 50 years, sophisticated
treatment modalities, technology, and care
philosophies have evolved to promote a strong
patient-centered care ethic coupled with
technological complexity.
The cost of delivering care to the critically ill
continues to rise. The Society of Critical Care
Medicine (2013a) identified increasing costs of
critical care medicine in the United States, with
current projections of $81.7 billion (13.4% of
hospital costs) in the care delivery of over 5
million patients annually in the nation’s critical
care units.
Organization of critical care
delivery
Haupt et al. (2003) published guidelines for
delivering
critical
care
based
on
a
multidisciplinary review of the literature and
writing panelists with representation from
important critical care providers including
32
physicians, nurses, pharmacists, respiratory
therapists, and other key critical care team
representatives. A three-level system of
intensive care unit (ICU) care was promoted in
these guidelines, acknowledging various ICU
care systems based on the availability of key
personnel,
educational
preparation,
certification,
and
fundamental
skill
requirements. These general guidelines for
hospitals in establishing and maintaining
critical care services assigned levels of care as
follows:
Level I care: units that provide medical
directorships with continual availability of
board-certified intensivist care and
appropriate minimal preparation
recommendations for all key and support
personnel.
Level II care: comprehensive care for
critically ill but unavailability of selected
specialty care, requiring that hospitals with
units at this level have transfer agreements
in place.
Level III care: units that have the ability to
provide initial stabilization and/or care of
relatively stable, routine patient conditions.
Level III units must clearly assess
limitations of care provision with
established transfer protocols (Haupt et al.,
2003, p. 2677).
33
Emphasis on intensivist medical management,
diagnostic testing availability, and specialty
interventional availability guides hospitals to
provide optimal care to the critically ill. This
has also been supported by the Society of
Critical Care Medicine (SCCM, 2013a). Haupt et
al. (2003) also made recommendations for
graduate education and/or certification by
critical care nursing managers within the
leadership structure. Transfer protocols for
higher levels of care were recommended if
selected life-saving services were unavailable,
suggesting that protocols be incorporated into
patient management systems in all hospitals
without the full range of service based upon
these guidelines. Despite the fact that these
guidelines were advanced over 10 years ago,
critical care practice remains diverse across the
nation due in part to the availability of key
personnel,
state
emergency
system
organization, system restrictions due to
population and area coverage, and cost
constraints. Emergency management and
trauma support guidelines have been advanced
by the American College of Surgeons (ACS)
though the Advanced Trauma Life Support
courses and guidelines for the transfer of
patients in rural settings are also published on
the ACS web site (Peterson and the Ad Hoc
Committee on Rural Trauma, ACS Committee
on Trauma, 2002).
34
Monitoring and surveillance in
critical care
In the care of critically ill patients, the use of
monitoring technology to support care is
central to evidence-based practice. Research on
the frequency and types of monitoring that
affect the best patient outcomes is growing.
Selected technologies, such as the use of
pulmonary artery catheters in the critically ill,
have been studied extensively. But the rapid
growth of new technologies for monitoring at
the bedside are often labor-intensive, requiring
considerable nursing time to set up and manage
to ensure good outcomes. In addition, ethical,
humane application of technology must be
continually considered so that the effect of
intrusive or invasive technology is continually
monitored in individualized care (Funk, 2011).
Effective monitoring requires familiarity with
the patient’s condition and preferences, the
equipment, the processes inherent in obtaining
the data, and the interpretation of monitored
data, all affected by potential error in
acquisition and management. Monitoring
allows for the calculation of critically ill
patients’ physiological reserve and effectiveness
of interventions but also carries the caveat that
practitioners must be familiar with the pitfalls
associated with data interpretation commonly
found in all areas of acute and critical care
practice (Andrews and Nolan, 2006).
35
Young and Griffiths (2006) reviewed clinical
trials monitoring acutely ill patients and
observed that “to display data which cannot
influence the patient’s outcome might increase
our knowledge of disease processes but does
not directly benefit the monitored patient. Nor
is it harmless, more information brings with it
more ways to misunderstand and mistreat” (p.
39). More monitoring may not be the answer to
improving the treatment of critically ill persons
but individualized monitoring of the right
parameters to guide therapy and improve
patient outcomes is the goal of the critical care
team. Revolutionary changes in patient
outcomes have been obtained with the
development of selected technology, including
pulse oximetry, bispectral index for depth of
anesthesia, and noninvasive measurement of
cardiac output and stroke volume (Young and
Griffiths, 2006). Despite the expansiveness of
monitoring, many have noted the paucity of
evidence of its effectiveness. Particularly in the
arena of hemodynamic monitoring, studies
have been equivocal regarding the effectiveness
of monitoring data to influence patient
outcomes (see Chapter 5).
Surveillance
Kelly (2009) studied nursing surveillance and
distinguished monitoring from surveillance by
noting that surveillance informs decision
making and involves action steps that stem
36
from more passive monitoring. Kelly (2009)
defined surveillance as “a process to identify
threats to patients’ health and safety through
purposeful
and
ongoing
acquisition,
interpretation, and synthesis of patient data for
clinical decision making in the acute care
setting” (p. 28). Surveillance is a core role of
critical care; while not unique to nursing,
surveillance is applied continuously in critical
care units worldwide. Henneman, Gawlinski,
and Giuliano (2012) identified surveillance as a
nursing intervention critical to patient safety. In
a review of practices recently studied in acute
and critical care nursing, Henneman,
Gawlinski, and Giuliano (2012) examined the
use of checklists, interdisciplinary rounds, and
other
clinical
decisional
support
and
monitoring systems important to surveillance
and prevention of errors.
The need for monitoring systems that produce
reliable and accurate data has never been more
urgent. Monitoring systems should be designed
to foster action and supportive care to improve
patient and family experience and physiological
outcomes for patients. Practices that do not
improve
patient
outcomes
should
be
eliminated. In addition, clinicians need to help
patients and family members understand
monitoring systems. Continual assessment of
changing conditions, critical reflection, critical
reasoning, and clinical judgment are all
supported with the use of appropriate
37
technology (Benner, Hughes, and Sutphen,
2008). Safe care practices depend on these
habits of the mind as well as reliable and
accurate technology. The potential for error is
evident at many junctures in today’s complex
hospital systems and the critical care unit is the
hub of such concentrated complexity, making
surveillance essential for safe patient care.
Research on monitoring and surveillance is
increasing. Schmidt (2010) studied the
concepts of surveillance and vigilance, and
identified the basic social process of nursing
support for patients in a critical care
environment, ensuring continual vigilance and
protective action to ensure safety. Yousef et al.
(2012) examined continuous monitoring data in
326 surgical trauma patients to determine
parameters associated with cardiorespiratory
instability. These were defined as heart rate less
than 40/min or greater than 140/min;
respirations less than 8/min or greater than 36/
min; SpO2 less than 85%; and blood pressure
less than 80 mmHg, greater than 200 mmHg
systolic, or greater than 110 mmHg diastolic.
Patients who remained clinically stable versus
those who had even one period of instability
were more likely to have more comorbidities, as
measured by the Charlson Comorbidity Index.
In earlier work, these authors found that 6.3 h
ensued between periods of cardiorespiratory
instability and activation of a rapid response
team (RRT) (Hravnak et al., 2008). In these
38
studies, automated, continuous monitoring
recorded and validated in the clinical
monitoring system strengthened the data
validity, including automated blood pressure
measurements measured at least every 2 h.
Clear
consideration
for
technology
advancement and the effects on both nursing
practice and patient outcomes is needed.
Nursing certification and
competency in critical care units
One method of moving toward more consistent
and safe practice involves certification in
critical care practice. All nurses practicing in
the ICU environment have curricula and
orientation programs, the ability to become
certified in the care of the critically ill, and, in
the case of the ACNPs and CNSs, the ability to
attain national certification and advanced
practice licensure. Does national certification
ensure quality care? Kaplow (2011) identified
the value associated with nursing certification,
including the value to patients and families,
employers, and individual nurses, noting that
certification validates specialty practice and
competency. Research is insufficient in linking
certification to improved patient outcomes but
denotes a level of professionalism and
recognition for increasing education and
competency (Kaplow, 2011). Coverage of the
many contributions of advanced practice nurses
39
to patient outcome measures will be explored in
the following sections.
Studies have shown links between nursing
certification and patient satisfaction with care
as well as nurses’ job satisfaction (Wade, 2009).
Fleischman, Meyer, and Watson (2011)
reviewed and highlighted best practices to
create a culture of certification across
institutions in the United States including
fostering supportive environments, recognition,
and improved research utilization as identified
best practices in critical care environments.
Wade (2009) identified a sense of increased
collaborative practice and empowerment
among certified nurses. Further work is needed
to validate patient outcomes associated with
certification.
Overcoming barriers to integration of research
at the bedside remains a challenge to all
providers concerned with improved quality of
critical care delivery (Leeman, Baernholdt, and
Sandelowski, 2007; Penz and Bassendowski,
2006). The use of improved educational
strategies to better prepare practitioners for
evidence-based practice guidance (Penz and
Bassendowski, 2006) and more refined change
strategies, including coordination across
disciplines, outcome-focused change, and
methods to increase behavioral control, such as
change leaders or champions, is recommended
(Leeman, Baernholdt, and Sandelowski, 2007).
40
In rapidly changing environments such as
critical care units, sustained change is difficult
to maintain and improved systems are needed
for better integration of evidence-based care.
Professional organizations often lead the way in
research to practice innovation. The American
Association of Critical Care Nurses (AACN,
2013a) has developed a series of practice alerts,
available as easy pdf file downloads with
selected power point slides for teaching care
providers. These are frequently updated by
leading researchers in the field and incorporate
current evidence for application to practice.
Mallory (2010) reported on strategies used by
the Oncology Nurse Society (ONS) to promote
evidence-based practices for translational
research (see Fig. 1.1). Adoption of clinical
practice guidelines is not a simple process and
often requires the attention of advanced
practice nurses and other team members
dedicated to attaining a high standard of care
and a strong method to ensure sustainable
change.
41
Figure
1.1
processes.
Knowledge
transformation
Adapted from Mallory (2010, pp. 280–284).
Explosive growth has occurred in the
application of evidence-based models to guide
education and practice. While too numerous to
highlight within this book, selected models
applied frequently to critical care practice
include the Iowa Model (Titler et al., 2001) and
the Johns Hopkins Model (Newhouse et al.,
2007).
US national critical care
organizations
The AACN and the SCCM have a long history
fostering
collaborative
practice
and
improvement of outcomes for critically ill
patients. Vibrant and patient-centered, these
42
organizations work to further the science and
practice of members and share a commitment
to the advancement of the art and science of
critical care practice, including the role of
nurses in improving patient outcomes and
treatment modalities.
American Association of Critical Care
Nurses
The AACN promulgates nursing standards and
is affiliated with a certification corporation
dedicated to certification of nurses in critical
care (AACN, 2013b). With a focus on promotion
of patient-centered care and support for critical
care nursing practice, the AACN endorses three
major advocacy initiatives, including healthy
work environments, end-of-life care, and
staffing/workforce
development.
Current
certifications available through the AACN
certification
program
include
specialty
certifications in acute/critical care nursing
(adult, neonatal, or pediatric), earning critical
care registered nurse (CCRN) certification;
CCRN-E, a tele-ICU version; adult progressive
care certified nurse (PCCN) credential; and a
certified nurse manager and leader (CNML)
credential. Subspecialty certifications are also
available in Certification in Cardiac Medicine
(CMC) and adult cardiac surgery (cardiac
surgical certification, CSC). Advanced practice
certifications are transitioning to the consensus
model certifications of Adult-Gerontology Acute
43
Care
Nurse
Practitioner
Certification
(ACNPC-AG) and ACCNS, CNSs (wellness
through acute care), available as gerontology,
pediatric, and neonatal designations. Adult
advanced practice certification is currently
available as adult ACNPC or adult, neonatal, or
pediatric versions of the acute care certification
of clinical nurse specialist (CCNS) exam (AACN,
2013b). The latter two certifications will
continue to be available for renewal but
candidates should see the AACN web site for
guidance concerning certification eligibility.
Certification programs are evaluated every 5
years and are based on competency
assessments.
Society of Critical Care Medicine
The SCCM promotes excellence in patient care,
education, research, and advocacy in the care of
critically ill patients. The SCCM self-identifies
as the only organization to represent all
professional members of the critical care team
and has a membership of nearly 16 000 in over
100 countries (SCCM, 2013b). The SCCM web
site includes a compilation of evidence-based
guidelines directly applicable to the care of
critically ill patients. There are also podcasts
and webinars available at no charge along with
other practitioner resources.
44
Acute care advanced practice
nursing
As the role of the advanced practice nurse has
evolved over the past several decades,
implementation of the role differs worldwide.
Mantzoukas and Watkinson (2006) sought to
clarify generic features of advanced nursing
practice through a review of the international
literature. In their summary, consistent
features included (i) the use of knowledge in
practice, (ii) critical thinking and analytical
skills,
(iii)
clinical
judgment
and
decision-making skills, (iv) professional
leadership and clinical inquiry, (v) coaching
and mentoring skills, (vi) research skills, and
(vii) changing practice (Mantzoukas and
Watkinson, 2006, p. 28).
Implementation of nurse practitioners (NPs)
and CNSs in critical care varies across the
United States. While growth in these advanced
practice roles is expected, care delivery and role
implementation often vary regionally and are
often driven by physician and nurse practice
patterns, hospital initiatives, and financial
support. Kleinpell and Hudspeth (2013)
reviewed terminology and organizational
frameworks for scope of practice in critical care
advanced practice roles. Competencies and
national models are reviewed with clarification
on the scope of practice of an advanced practice
45
registered
ACNPs.
nurse
(APRN),
particularly
for
Becker et al. (2006) reported on the national
task force survey for delineation of the work of
advanced practice critical care nurses in an
effort to clarify roles of the ACNPs and CNSs.
The specific aims of this study were to reveal
criticality and frequency ratings for 65 APRN
activities and to compare spheres of influence
distinctive to each role. Significant distinctions
included a focus on individual patients in the
role of ACNP (74 versus 25.8% for CNS) and
relatively small amount of advanced practice
nursing time spent on interventional skills in
both APRN roles. Eight activities were reported
with greater frequency by ACNPs compared
with CNSs: developing/implementing and
modifying the plan of care; prescribing
medications and therapeutics; comprehensive
history and physical examinations; differential
diagnoses; ordering diagnostic studies; making
referrals; performing invasive procedures; and
empowering patients and families as own
advocates (Becker et al., 2006, p. 142).
Clinical nurse specialists
The CNS’s role is focused on three spheres of
influence advanced by the National Association
of Clinical Nurse Specialists (NACNS): patients
and families, nurses/nursing practice, and
organization/systems. It incorporates the
46
AACN Synergy Model (AACN, 2013b), and the
competencies of advanced practice nursing
presented by Hamric, Spross and Hanson
(2009). Outcome assessment in complex
environments has become an important part of
advanced practice for CNSs and integral to
graduate programs.
The NACNS (2009) developed the Core
Practice Doctorate Clinical Nurse Specialist
Competencies in collaboration with other
stakeholders. These have been endorsed by a
number of national organizations (NACNS,
2009). In this document, expansion of
advanced practice competencies to the doctoral
level includes emphasis on expanded
translational
research,
interprofessional
collaboration, and many other competencies
identified by national organizations to advance
clinical nursing practice (NACNS, 2009). The
competencies that were advanced included
client sphere of influence, nurse and nursing
practice competencies, and organizational
systems competencies (NACNS, 2009).
Altmiller (2011) applied a framework of quality
and safety education for nurse competencies
using these spheres of influence for CNS
preceptors designed to bring transparency to
the many contributions made by CNSs to
hospital systems that improve care at the
bedside but are often difficult to track. These
include the influence of skilled CNSs in
47
precepting other nurses, building teamwork
and
collaboration,
implementing
evidence-based practice, quality improvement
practices, safety promotion through system
effectiveness, and informatics applications to
ensure effective communication, management
of knowledge, and foundational decision
making. These competencies were promulgated
by the Quality and Safety Education for Nurses
(QSEN) project, funded by the Robert Wood
Johnson Foundation in response to the initial
Institute of Medicine report targeting the
education of health professionals to improve
safety (Institute of Medicine, 2001; Hughes,
2008).
Acute care nurse practitioners
The evolution the ACNP’s role has been
attributed to workforce issues related to
restrictions in the hours medical students were
able to work during residencies (D’Agostino and
Halpern, 2010; Kleinpell, Ely, and Grabenkort,
2008; Weinstein, 2002). Among the newest NP
roles, ACNPs were first certified in 1975 (Becker
et al., 2006). Over time, advanced practice
nursing programs emerged with significant
variability across the United States. In the past
decade, significant progress has been made in
promoting
standard
terminology
and
educational guidelines for advanced practice
nurses (APRN Joint Dialogue Group Report,
2008). In these guidelines, endorsed by most
48
national nursing organizations, the four roles of
APRNs are confirmed (clinical nurse specialist,
certified registered nurse anesthetist, nurse
practitioner, and nurse midwife) and
educational guidelines have broadly changed to
an educational focus on patient population
rather than specialty tracks. APRN regulatory
standards encompass guidelines on licensure,
accreditation, certification, and education
(APRN Joint Dialogue Group Report, 2008),
addressed through established standards for
guidance on advanced nursing educational
program content in the United States. In these
guidelines, the specialty role is not
distinguished as a broad NP practice
categorization (e.g., ACNP, Oncology). The
APRN guidelines have evolved so that
widespread changes in certification are planned
for 2015 (National Task Force on Quality Nurse
Practitioner Education, 2012). ACNPs will
obtain certification as advanced practice nurses
(APRNs) with an adult/gerontology focus or a
pediatric focus through selected examinations
offered by the American Nurses Certification
Corporation (ANCC, 2013). The ANCC
identifies December 31, 2014, as the last date
for applications for certification as an ACNP. As
the NTF guidelines (2012) are implemented,
certification will move the ACNP role to an
APRN title with specialty exams focused on
adult/gerontology or pediatrics. Most ACNP
and Oncology educational programs have
strengthened the adult/gerontological or
49
pediatric population focus with continued
unique coursework to guide specialty practice.
Certification is currently required to obtain
state licensure as APRNs. Many current ACNP
programs require registered nurse licensure
and clinical experience in critical care prior to
entry into the NP track although a number of
programs nationally allow second baccalaureate
or higher degree entry and accelerated progress
over several years to graduation. Students
interested in becoming safe practitioners must
recognize the complexity of the critical care
environment and give careful consideration to
their own skills and capabilities when
examining educational options. The richness of
multiple learners with a variety of experience
adds value to the learning environment and
promotes multidisciplinary communication, an
important factor in critical care safe practices,
although this is an area that remains
understudied.
Kleinpell and Goolsby (2006) evaluated ACNP
practice identified by 635 national ACNPs from
survey data associated with the 2004 American
Academy of Nurse Practitioner database. The
majority of studies reviewed the impact of
ACNPs and physician assistants in acute and
critical care, ranging from evaluating specific
patient care and disease management outcomes
to communication, compliance with guidelines,
and other process management strategies.
Studies demonstrate similar patient outcomes
50
delivered by ACNPs and physician assistants
(PAs) in critical care settings although few
large-scale, randomized studies have been done
(Kleinpell, Ely, and Grabenkort, 2008). As the
ACNP role evolves and additional research
clarifies outcomes, integration within the
health-care team will be better elucidated.
As a relatively new role in critical care, the
ACNP role integration into systems has
generally enhanced patient satisfaction and
collaborative care practices (Cobb and Kutash,
2011; Howie and Erickson, 2002). Hoffman et
al. (2005) compared outcomes of care managed
in a subacute medical ICU to that provided by
resident physicians and found no differences in
length of stay, readmissions to critical care, or
number of patients weaned prior to discharge.
A growing role for APRNs is on hospitalist
teams (Kleinpell et al., 2008). Another
relatively recent addition to hospital practice,
hospitalist medicine generally represents
coverage of care for inpatients by internal
medicine, family practice, or pediatric
specialties. Over 40 000 hospitalists practice in
US and Canadian hospitals and continued
growth is expected (Society of Hospital
Medicine, 2012).
51
Critical care and ACNP outcomes
research
Within acute care environments, ACNPs may
practice in areas beyond the traditional ICU
environment. D’Agostino and Halpern (2010)
studied the integration of ACNPs into an
oncology practice, reviewing educational and
support programs for staff to aid transitions to
specialty practice. Using a multidisciplinary
model, including departments of nursing,
anesthesiology, and critical care medicine, the
authors provide a structure for planned
implementation of the role. Due to regional
shortages of ACNPs, other NP specialists,
including family NPs and adult NPs may enter
NP programs with experience in areas of
traditional nursing such as critical care.
Following graduation, these NPs may practice
in acute care environments or specialty office
practices, making it difficult to track practice
patterns among ACNPs nationally.
Kleinpell, Ely, and Grabenkort (2008) analyzed
research on nonphysician providers in acute
and critical care settings, focusing on PAs and
NPs. In a systematic review of 145 manuscripts,
only two randomized control trials (RCTs) were
found by Cooper et al. (2002) and Sakr et al.
(1999). Both of these RCTs were conducted in
the emergency department setting. While
support for the contributions of NPs and PAs to
critical care delivery was found among other
52
strong prospective studies, the level of evidence
remains weak and further studies are needed.
Further studies targeting dissemination of
practice models for advanced practice roles;
ICU patient outcome impact of advanced roles;
research regarding supply and demand of
staffing needs in the ICU, including intensivist
and midlevel providers; and studies on billing
of services are recommended (Kleinpell, Ely,
and Grabenkort, 2008).
Kleinpell (2013) extensively reviewed outcome
research in advanced practice nursing,
comparing studies across APRN roles. This text
provides a strong contribution to the literature
on effectiveness of APRNs, summarizing
patient and care-related outcomes including
studies
on
economic
effectiveness.
Overwhelmingly, APRN contributions to care
are demonstrated to be strong and equal or
superior to the care of other practitioners such
as physicians or PAs. In many studies, the
addition of an NP team member resulted in
improved care delivery, shorter lengths of
hospital stay, and reduced costs (Kleinpell,
2013). As the role of the ACNP remains
relatively new and evolving, further outcome
studies are needed that highlight the
cost-effectiveness of these roles such as those
attained in specific settings (e.g., cardiac
catheterization
laboratories,
surgical
or
transplant services) to broader patient
treatment lines (e.g., care of congestive heart
53
failure patients and patients on prolonged
ventilator management).
As critical care settings evolve, advanced
practice nurses and researchers continue to
examine changing health-care systems. Burman
et al. (2009) recommend a reconceptualization
of the core elements of NP education and
practice, emphasizing stronger classroom and
clinical coursework in health promotion and
disease prevention. Emerging programs for
patients with chronic diseases such as heart
failure and chronic obstructive pulmonary
disease (COPD) are potentially life-changing as
chronic diseases account for 60% of all deaths
worldwide.
Advanced
practice
nurses,
particularly those with strong education and
practice in critical care settings, may contribute
significantly to these evolving models of care.
Evolution of families in the critical
care unit
In the early days of critical care units, an ethic
of isolation of patients emerged, attributable to
the beliefs on rest and healing. Familes were
often considered a distraction with the potential
to interfere rather than support the healing
process. AACN and SCCM have joined in
promoting less restrictive visiting privileges in
the critical care arena. In 2007, Davidson et al.
promulgated clinical practice guidelines for
support of the family in the patient-centered
54
ICU based on an extensive literature review.
Categories of studies reviewed and clinical
practice recommendations were offered in 10
areas: decision-making, family coping, staff
stress related to family interactions, cultural
support of the family, spiritual and religious
support, family visitation, family environment
of care, family presence on rounds, family
presence at resuscitation, and palliative care.
Most recommendations are based on case series
or expert opinion rather than controlled studies
but further research needs are highlighted. Of
the 43 recommendations given within these
guidelines, supportive references and overviews
of current practice are analyzed carefully,
making these important to new and seasoned
practitioners in the critical care environment
(Table 1.1).
Table 1.1 Family support in the ICU.
Adapted from Davidson et al. (2007).
Recommendations
(Davidson et al.,
2007)
Sample
Evidence
recommendation grade
1
Decision making in B
the ICU is based on
a partnership
between the
patient, his or her
appointed
surrogate, and the
Decision-making
55
Recommendations
(Davidson et al.,
2007)
Sample
Evidence
recommendation grade
multiprofessional
team (p. 608)
2
Family coping
ICU staff receives
C
training in how to
assess family needs
and family
members’ stress
and anxiety levels
(p. 609)
3
Staff stress related
to family
interactions
The
C
multiprofessional
team is kept
informed of
treatment goals so
that the messages
given to the family
are consistent,
thereby reducing
friction between
team members and
between the team
and the family (p.
610)
4 Cultural support of On request or when C
the family
conflict arises due
to cultural
differences in
values, when there
56
Recommendations
(Davidson et al.,
2007)
Sample
Evidence
recommendation grade
is a choice of
providers, the
provider’s culture is
matched to the
patient’s (p. 610)
5
Spiritual and
religious support
Spiritual needs of
the patient are
assessed by the
health-care team,
and findings that
affect health and
healing
incorporated into
the plan of care (p.
612)
C
6 Family visitation
Open visitation in B
the adult intensive
care environment
allows flexibility for
patients and
families and is
determined on a
case-by-case basis
(p. 613)
7
Improve patient
B
confidentiality,
privacy, and social
support by building
Family
environment of
care
57
Recommendations
(Davidson et al.,
2007)
Sample
Evidence
recommendation grade
ICUs with
single-bed rooms
that include space
for the family (p.
613)
8 Family presence on Parents or
B
rounds
guardians of
children in the ICU
are given the
opportunity to
participate in
rounds (p. 614)
9 Family presence at
resuscitation
Institutions develop C
a structured
process to allow the
presence of family
members during
cardiopulmonary
resuscitation of
their loved one that
includes a staff
debriefing (p. 615)
10 Palliative care
Assessments are
D
made of the family’s
understanding of
the illness and its
consequences,
symptoms, side
58
Recommendations
(Davidson et al.,
2007)
Sample
Evidence
recommendation grade
effects, functional
impairment, and
treatments and of
the family’s ability
to cope with the
illness and its
consequences.
Family education
should be based on
the assessment
findings (p. 616)
Evidence grades: B, systematic reviews or
strong cohort studies; C, case series or weak
cohort studies; D, expert opinion.
Research has demonstrated improvements in
patient comfort and enhanced support when
family presence is less restrictive, including
family presence during resuscitation and
ventilator weaning (Doolin et al., 2011; Happ et
al., 2007). The team must always seek to
balance the presence of families and others who
are significant in the patient’s life with patient’s
care needs. The context of family presence must
be carefully evaluated since prior relationships
with family members may drive whether
patients view family presence as helpful or
harmful. In their ethnographic research of
family presence during weaning from
59
mechanical ventilation, Happ et al. (2007)
noted that clinicians reported that calming or
soothing presence including touch and gentle
talk was supportive to patients undergoing
weaning trials, while a “tense demeanor,
hovering, being overly close, and asking the
patient about symptoms, activity tolerance, or
weaning
progress
were
considered
a
hinderance” (p. 56). Many studies have
confirmed the needs of families as well as
patient-identified desire to have family and/or
significant others present in the ICU.
Henneman and Cardin (2002) offered a 10-step
approach to improve family-centered care in
the ICU with a focus on multidisciplinary
involvement and inclusion of the philosophy
from orientation of new staff members to initial
encounters with family members of patients
admitted to the ICU. They suggest that clarity
be first reached among the multidisciplinary
team with endorsement of a family-centered
philosophy that should be systematized in a
unit. Family-centered care is much more than
simple visitation policies and involves true trust
and collaboration between patients, their
families, and the care team.
Doolin and colleagues. (2011) credit Foote
Hospital in Jackson, Michigan, as the first to
implement a formal hospital policy supporting
family presence during resuscitation. They offer
a strong review of the literature guiding family
presence, including a review of attitudes and
60
beliefs of patients, caregivers, and family
members and historical issues associated with
hospital policies concerning family presence. A
strong advocacy role for APRNs in promoting
policies that support family presence and other
evidence-based interventions in critical care
areas is needed.
Progression and development of
rapid response teams
RRTs have emerged over the past 10 years as a
means to improve patient safety and reduce
failure to rescue situations. Sonday, Grecsek,
and Casino (2010) reviewed the role of NPs in
the application of RRTs, describing an
approach driven by an ACNP model. The
authors observed that this approach provides
for patient-centered care by relying on expert
assessment, critical thinking, and medical
management
skills
rather
than
static
protocol-driven management. In a primary
physican/ICU nurse mode, Buist et al. (2002)
retrospectively analyzed the patient outcomes
associated with the implementation of a
medical emergency team following unexpected
cardiac arrests in hospitals. Examining data
from 1996 compared with 1999, they found
significant reductions in cardiac arrests and
reductions in mortality from 77 to 55%
following the introduction of medical
emergency teams within the hospital.
61
Comparative odds ratio for cardiac arrest with
the team in place was 0.50 (0.35–0.73) (Buist
et al., 2002).
The use of integrated systems has grown in the
intensive care environment. Tarassenko, Hann,
and Young (2006) examined the use of
integrated monitoring systems for early
warning of patient deterioration and activation
of RRTs. In one evaluation of a system designed
to trigger activation of the team, an early
warning system trended five vital sign measures
and data fusion to create a single status
measure. Patients’ heart rate, blood pressure,
oxygen saturation, skin temperature, and
respiratory rate were combined to produce this
single measure. Most alerts were found to be
valid but other important measures of
evaluation, including mental status and urine
output, remained dependent on regular
assessments.
Cherry and colleagues (2009) examined a
response team designed to activate for a series
of patient conditions, including changes in vital
signs, cardiac rhythm, mental status,
oxygenation decline, altered fluid status, and
symptoms such as chest pain, dyspnea, or
stroke signs. After implementation, improved
outcomes included timeliness of response of the
team within 10 min and significant reductions
in non-ICU cardiac arrests.
62
Critical care practice continues to evolve and
the role of advanced practice nursing in patient
care continues to grow and be refined. While
practice patterns and financial issues often
dictate the implementation of these roles at the
bedside, advanced practice nurses will
increasingly play a role in surveillance,
treatment, and safety of critically ill patients in
the future.
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72
Chapter 2
Vital measurements and
shock syndromes in critically
ill adults
Kathy J. Booker1 and Laura Kierol Andrews2
1
School of Nursing, Millikin University,
Decatur, IL., USA
2
Yale School of Nursing, Orange, CT., USA
Monitoring basic vital signs
Analysis of vital signs is a cornerstone of
management of the critically ill adult patient.
Subtle changes that might represent normal
shifts in a healthy person may signal early
decline for those in critical states. Monitoring
vital signs is one of the most common
techniques employed continuously in critical
care units and careful attention should be given
to setting alarms so that they are informative
and not overly sensitive. Alarms that
continually discharge have a negative influence
on care and may be turned off as a nuisance,
placing patients at increased risk. Due to the
complexity of direct care needs, nurses may
find it difficult to be attentive to monitoring
systems at all times even when caring for
73
patients one-on-one. An American Association
of Critical Care Nurses (AACN) practice alert on
alarm management was issued in 2013,
recommending careful attention to appropriate
skin preparation for electrodes, customization
of alarms in bedside monitoring systems to
patient condition and surveillance needs
(AACN, 2013).
Interestingly, how often to monitor and record
vital signs has been studied infrequently. In
addition, the use of continuous monitoring and
trending capabilities of bedside systems
requires considerable foresight and evaluation
due to errors in monitoring from patient
movement, loose electrodes, and other
technical issues. In a systematic review of vital
sign measurement in hospitalized patients,
Evans, Hodgkinson, and Berry (2001) noted
that most recommendations for frequency are
based on expert opinion and tradition with little
research-based
support
for
monitoring
frequency linked to patient outcomes.
Schumacher (1995) studied 766 postoperative
patients’
vital
sign
monitoring
and
recommended measurements 15 min after
return from postanesthesia units, followed by
30 min × 2, 1 h, then every 4 h × 4. These
recommendations continue to be employed in
postoperative management today and further
research is needed, particularly evaluations of
frequency of intermittent methods as
harbingers of patient decline.
74
Evans, Hodgkinson, and Berry (2001) also
reviewed the literature support for the addition
of a fifth vital sign, including the potential
addition of nutritional status, body mass index,
spirometry, orthostatic blood pressure (BP)
changes, pulse oximetry, and smoking status.
Of these, pulse oximetry showed considerable
promise as an addition that may influence
patient outcomes (Evans, Hodgkinson, and
Berry, 2001; Mower et al., 1995). Pulse
oximetry is also continuously monitored in
most intensive care unit (ICU) settings today
and is often a key driver of respiratory
interventions. Others have suggested that pain
assessment should comprise the fifth vital sign
(Merboth and Barnason, 2000).
Future
research
should
examine
the
effectiveness
of
increasingly
integrated
monitoring systems used for critically ill
patients to reveal best practices for stronger
surveillance and prevention of physiological
decline. In addition to the rapid growth of
interventional protocols, technology has
allowed for most vital measures to be
continuously displayed but accuracy is not
always ensured. With thousands of devices and
specialized equipment in use in ICUs across the
nation, safety and error prevention must be a
priority (Mattox, 2012). Device safety involves
many important aspects and clinicians must
also master technology evaluation skills and
continuously question the accuracy produced
75
by bedside and clinical evaluation systems
(Henneman, 2010). Implementation of new
technologies should always require careful
system analysis and involvement of nurses
caring for patients.
In this chapter, standard vital sign
measurement and monitoring for shock states
will be reviewed. Overall, the level of evidence
for frequency of standard vital measures, while
ubiquitous to critical care, remains relatively
low. Overuse of technology increases staff
workload while not necessarily improving
patient outcomes. Selected elements of shock
management and the growth of care bundling
have moved evidence-based practices to
moderate to high levels. Monitoring and
surveillance in shock conditions will also be
reviewed.
Temperature monitoring
In general, the most accurate methods of
measuring temperature include the use of
pulmonary artery thermistor, urinary bladder
probes, esophageal probes, and rectal probes
(O’Grady et al., 2008). The Heart and Stroke
Foundation of Canada (2004) issued a position
statement recommending bladder probe or
pulmonary artery thermistor monitoring as the
most reliable in therapeutic hypothermia
patient monitoring. Most ICU monitoring
systems have probe connectors so that core
temperature may be continuously trended with
76
other bedside vital signs data although today
pulmonary artery catheters are used less
frequently in medical ICU settings.
Temperature monitoring options range from
standard intermittent oral, skin, and tympanic
measurements to more invasive continuous
monitoring with sensors placed in the bladder
or bloodstream as part of indwelling catheters
or centrally introduced lines, respectively.
Accuracy varies considerably by site. Generally,
lines placed internally in core areas such as the
bladder or bloodstream are more reflective of
core temperature than those measured
externally; however, accuracy ranges should be
evaluated carefully through a review of
manufacturing guidelines and confirmed by
multiple techniques when temperature change
is in question. O’Grady et al. (2008) published
guidelines for the evaluation of new
temperature elevations in critically ill patients,
recommending that assessment findings rather
than automatic blood testing should guide
management of temperature elevations. Blood
culture techniques and interventions should be
implemented when noninfectious causes for
temperature elevation have been ruled out
(O’Grady et al., 2008) (see Table 2.1).
Table 2.1 Recommendations for measuring
temperature.
Adapted from Frommelt et al., 2008; Nonose et
al., 2012; O’Grady et al., 2008).
77
Elements Monitoring recommendation
Method
and site
Temperature measurements are
most accurate using intravascular,
esophageal, or bladder
measurements (Nonose et al.,
2012; O’Grady, 2008); Tympanic
measurement should be avoided
in adults and children (Frommelt,
Ott, & Hays, 2008; Nonose et al.,
2012). Rectal, oral, and tympanic
may be used, in that order if IV,
esophageal or bladder monitoring
not available (O’Grady et al.,
2008). Axillary measurements,
temporal artery estimates, and
chemical dot thermometers
should not be used in the ICU
(level 2). Rectal thermometers
should be avoided in neutropenic
patients (O’Grady et al., 2008)
(level 2).
Monitoring Safe practices of calibration and
device
manufacturer’s guidelines should
be followed (O’Grady et al., 2008)
(level 2).
Infection
control
All practices associated with
temperature monitoring must
employ safe instrument usage and
handwashing to limit
microorganism spread (O’Grady
et al. 2008) (level 2).
78
Elements Monitoring recommendation
Site
The site of temperature
measurement should be recorded
with the temperature in the chart
(level 1).
Further
A new onset of temperature >/=
diagnostics 38.8 °C or < 36 °C <36 °C is a
reasonable trigger for a clinical
assessment but not necessarily a
laboratory or radiologic
evaluation for infection (O’Grady
et al., 2008) (level 3).
Society
of
Critical
Care
Medicine
recommendation levels: level 1, convincingly
justifiable on scientific evidence alone; level 2,
reasonably justifiable by available scientific
evidence and strongly supported by expert
critical care opinion; level 3, adequate scientific
evidence is lacking but widely supported by
available data and expert critical care opinion
(O’Grady et al., 2008), p. 1331–1332.
Schey, Williams, and Bucknall (2010) reviewed
the use of core–peripheral temperature
gradients and the research linking this measure
to cardiac output changes. This technique has
been studied for decades but well-designed
definitive studies have not been conducted. In
the largest study of over 1000 patients in
cardiogenic shock, distal skin temperature was
not prospectively obtained; cold periphery and
79
oliguria served as comparisons to cardiac
output and no direct correlation was found
(Menon et al., 2000). Schey, Williams, and
Bucknall (2010) noted that confounding
factors, small enrollments, and the use of
multiple methods precludes firm conclusion on
the use of core–peripheral temperature
comparative research and requires further
prospective trials. Frequency outcome of vital
sign monitoring remains understudied.
Hypothermia
Over the last decade, the use of hypothermia
protocols following cardiac arrest has evolved
as an evidence-based practice (Nolan et al.,
2003; Nunnally et al., 2011; Peberdy et al.,
2007; Sasson et al., 2011). Improved
neurological outcomes have been associated
with the use of hypothermia protocols initiated
as soon as possible following successful return
of spontaneous circulation (ROSC) (Kagawa et
al., 2010; Nunnally et al., 2011; Peberdy et al.,
2007; see Table 2.2). The targeted temperature
for hypothermia is 32–34 °C for 12–24 h post
cardiac arrest following ROSC (Nunnally et al.,
2011; Peberdy et al., 2007). While no specific
method of hypothermia induction is endorsed,
the published guidelines support the use of
cooled isotonic fluid administration and
external cooling devices and monitoring of core
temperature during the cooling phase.
Prospective trials have also validated cooling
80
patients using ice packs, intravascular cooling
devices, and selected treatments such as cooling
helmets or cool air tents (Australian
Resuscitation
Council,
New
Zealand
Resuscitation Council, 2011). Additional critical
monitoring elements include prevention and
detection of shivering and early management
and treatment of seizures.
Table 2.2 Beneficial effects of hypothermia.
BioMed Central Open Access: Sinclair, HL, &
Andrews PJD (2010). Bench-to-bedside review:
hypothermia in traumatic brain injury, 2010,
14, 204.
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
Prevention of
apoptosis*
Ischaemia can
induce apoptosis
and
calpain-mediated
proteolysis. This
process can be
prevented or
reduced by
hypothermia.
Hours
to days
to even
weeks
81
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
Reduced
mitochondrial
dysfunction and
improved energy
homeostasis†
Mitochondrial
Hours
dysfunction is a
to days
frequent
occurrence in the
hours to days after
a period of
ischaemia and
may be linked to
apoptosis.
Hypothermia
reduces metabolic
demands and may
improve
mitochondrial
function.
Reduction in free Production of free Hours
radical
radicals (for
to days
production†
example,
superoxide,
peroxynitrate,
hydrogen
peroxide, and
hydroxyl radicals)
is typical in
ischaemia.
82
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
Mild-moderate
(30–35 °C)
hypothermia is
able to reduce this
event.
Mitigation of
reperfusion
injury†
Cascade of
Hours
reactions
to days
following
reperfusion, partly
mediated by free
radicals but with
distinctive and
various features.
These are
suppressed by
hypothermia.
Reduced
permeability of
the blood-brain
barrier and the
vascular wall and
reduced oedema
formation*
Blood-brain
Hours
barrier
to days
disruptions
induced by
trauma or
ischaemia are
moderated by
hypothermia. The
same effect occurs
83
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
with vascular
permeability and
capillary leakage.
Reduced
permeability of
cellular
membranes
(including
membranes of
the cell nucleus)†
Decreased leakage Hours
of cellular
to days
membranes with
associated
improvements in
cell function and
cellular
homeostasis,
including decrease
of intracellular
acidosis and
mitigation of DNA
injury.
Improved ion
homeostasis
Ischaemia induces First
accumulation of
minutes
excitatory
to 72 h
neurotransmitters
such as glutamate
and prolonged
excessive influx of
Ca2+ into the cell.
84
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
This activates
numerous enzyme
systems (kinases)
and induces a
state of
hyperexcitability
(exitotoxic
cascade) that can
be moderated by
hypothermia.
Reduced
metabolism*
Cellular oxygen
Hours
and glucose
to days
requirements are
reduced by 5–8%
per °C decrease in
temperature.
Depression of the
immune response
and various
potentially
harmful
pro-inflammatory
reactions*
Sustained
First
destructive
hour to
inflammatory
5 days
reactions and
secretion of
pro-inflammatory
cytokines after
ischaemia can be
blocked or
85
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
mitigated by
hypothermia.
Reduction in
cerebral
thermopooling*
Some areas in the Minutes
brain have
to days
significantly
higher
temperatures than
others. These
differences can
increase
dramatically after
injury with
temperatures that
are up to 2–3 °C
higher in injured
areas.
Hyperthermia can
increase the
damage to the
injured brain
cells; this is
mitigated by
hypothermia.
Anticoagulant
effects*
Microthrombus
formation may
86
Minutes
to days
Possible mechanisms underlying the
beneficial effects of hypothermia
Secondary
injury
Explanation
Time
frame
after
injury
add to brain injury
after CPR.
Anticoagulant
effects of
hypothermia may
prevent thrombus
formation.
Suppression of
epileptic activity
and seizures*
Seizures after
Hours
ischaemic injury to days
or trauma are
common and may
add to injury.
Hypothermia has
been shown to
mitigate epileptic
activity.
This table summarises potential beneficial
effects of hypothermia, based on experimental
and clinical studies.
*Some supporting evidence.
†Animal studies only.
CPR, cardiopulmonary resuscitation.
87
Since cardiac arrest often accompanies acute
myocardial infarction, rapid assessment of
electrocardiogram (ECG) changes and rapid
percutaneous intervention are recommended if
indicated following ROSC. While outcomes
have improved with the use of hypothermia
treatment,
implementation
of
rapid
hypothermia protocols is not consistent across
the nation and research is still needed for
optimal treatment protocols for managing
patients following cardiac arrest.
Complications of cooling
Hypothermia treatment can be risky and has
been associated with arrhythmias, infection,
and coagulopathies (Heart and Stroke
Foundation of Canada, 2004). During
hypothermia,
shivering
is
a
frequent
complication and must be treated to prevent
increased cerebral oxygen consumption, which
is estimated to be elevated by 40–100% during
shivering episodes (Sinclair and Andrews,
2010). In alert patients, progressive symptoms
that can be expected include the following:
36 °C: Increased activity attempting to warm
up, skin pale, numb, and waxy, muscles tense,
fatigue, and signs of weakness.
34–35 °C: Uncontrolled intense shivering, still
alert but movements uncoordinated, and pain
and discomfort due to coldness.
88
31–33 °C: Shivering slows or stops, muscles
stiffen, mental confusion, apathy, speech
slowed and slurred, breathing slower and
shallow, drowsiness.
<31 °C: Skin cold, pupils dilated, extreme
weakness, slurred speech, exhausted, denies
problems, resists help, gradual loss of
consciousness, and progressive respiratory
arrest and arrythmias (Nunnally et al., 2011, p.
1116).
In patients who are comatose, heavily sedated,
or treated with paralytic agents, shivering may
be detected by additional monitoring, such as
bispectral
index
(BIS)
or
electroencephalography (EEG) monitoring. The
use of supplemental monitoring has not been
extensively
studied
and
evidence-based
guidelines are not available.
Hypothermia induction is used for other
applications in the critical care unit, including
control of severe hyperthermia induced by
heatstroke or malignant hyperthermia (MH), a
condition induced by a relatively rare triggered
response to anesthesic agents. In addition,
patients with neurologic conditions will often
have markedly elevated temperatures and
require cooling methods for temperature
reduction. These conditions have diverse
pathophysiologies but treatment is focused on
safe, rapid cooling. Hoedemaekers et al. (2007)
examined cooling methods in 50 adult ICU
89
patients randomized to one of the following five
methods: (1) conventional cooling with cold
intravenous infusions of 30 ml/kg, ice or
coldpacks; (2) cooling with water-circulating
blankets; (3) air-circulating cooling blankets;
(4) gel-coated external cooling device using
pads on the back, abdomen, and bilateral
thighs; and (5) intravascular cooling using a
single lumen central venous catheter inserted
into the femoral vein. If the target temperature
was not reached within 12 h, ice and cold packs
were supplemented. Hoedemaekers et al.
(2007) found that three cooling methods were
equally effective: water-circulating blankets,
gel-coated pads, and intravascular cooling.
Endovascular cooling was most effective at
maintaining the target temperature but was
also the most costly method. Conventional
cooling was shown to be ineffective, with failure
to reach target temperature in 60% of patients
randomized to this method.
Hyperthermia
Perspectives on fever have changed over the
past decade. In non-life-threatening infections,
fever may exert a delimiting effect on the
clinical condition, reducing days of infection.
However, in severe infections and sepsis, the
overwhelming state of systemic inflammation
and preexisting state of health make it difficult
to predict clinical outcomes associated with
fever and its treatment (Hasday, Fairchild, and
90
Shanholtz, 2000; Kiekkas et al., 2010). The
impact of fever on ICU mortality in 239
critically ill adult patients without cerebral
damage was studied and 44.8% developed fever
(Kiekkas et al., 2010). Fever alone was not
associated with mortality; however, peak
temperature at the higher ranges (39.3 °C and
above) resulted in higher ICU mortality than in
those with lower peak temperatures. Not
surprisingly, patients with higher acuity scores
had significantly higher mortality (p < 0.001,
OR 1.24). In this study, the lower respiratory
tract (76.9%), blood (15.4%), and abdomen
(7.7%) accounted for the primary sites of
infectious causes of fever. Given the associated
increased metabolic demand associated with
hyperthermia, conclusive evidence favoring
antipyretic therapy remains unclear but
temperature elevations continue to drive
therapy and remain an important assessment
parameter. Kiekkas et al. (2010) also evaluated
the effect of temperature elevation (≥38.3 °C)
on other vital parameters, including hourly
changes in mean arterial pressure (MAP), heart
rate (HR), and arterial oxygen saturation
during a 24-h period of intensive care
hospitalization. While statistically significant
changes in HR and MAP were found in this
study, the authors noted that the changes were
generally minor and did not represent clinically
significant morbidity.
91
Heatstroke management
Patients admitted for heatstroke present special
challenges in care. Bouchama, Dehbi, and
Chaves-Carballo
(2007)
studied
the
hemodynamic management associated with
cooling
patients
with
life-threatening
heatstroke, defined as temperatures over 40 °C.
Cooling by immersion in iced water was found
to be safe and effective in young healthy adults
with exertional heatstroke, but posed problems
in elderly patients. Ice packs, wet gauze sheets,
and use of fans were recommended as
reasonable alternatives in elderly patients and
consideration given to the use of dantrolene as
an adjunct therapy. In addition, Bouchama,
Dehbi,
and
Chaves-Carballo
(2007)
recommended
avoiding
antipyretics
in
heatstroke patients due to the potential of
coagulopathy or liver injury but identified the
paucity of research in this area.
Malignant hyperthermia
A condition that may develop during the
delivery of anesthetics or in the early
postoperative period, MH is a critical
emergency with elevations of core temperature.
Temperature elevations may reach 44 °C
(Rosenberg et al., 2007). Triggers include all
inhaled anesthetics and succinylcholine, a
muscle relaxant. MH is found in all parts of the
world and is linked to an autosomal-dominant
defect. Larach et al. (2010) reported initial MH
92
signs as hypercarbia, sinus tachycardia, and
masseter spasm along with elevations in
temperature.
Generalized
musculoskeletal
contraction and the development of respiratory
and/or metabolic acidosis are common.
Dantrolene remains the primary interventional
treatment for this condition, is lifesaving, and,
with careful fluid management during an acute
episode of MH, dantrolene is generally safe
(Brandom et al., 2011; Glahn et al., 2010).
Published guidelines for recognizing and
managing MH crisis including monitoring
temperature and treating complications have
been advanced by the European Malignant
Hyperthermia Group (Glahn et al., 2010).
These
include
measurement
of
core
temperature, routine anesthetic monitoring, IV
access, and minimum 24-h monitoring in the
ICU. Kim (2012) also reviewed these guidelines,
including clinical sign recognition (see Table
2.3).
Table 2.3 Clinical signs associated with
malignant hyperthermia.
(Adapted from Glagn et al. 2010).
Reproduced by permission of the Korean
Society of Anesthesiologists. © Korean Society
of Anesthesiologists.
Early signs
Metabolic
93
Inappropriately elevated CO2
production (raised end-tidal CO2 on
capnography, tachypnoea if breathing
spontaneously).
Increased O2 consumption.
Mixed metabolic and respiratory
acidosis.
Profuse sweating.
Mottling of skin.
Cardiovascular
Inappropriate tachycardia.
Cardiac arrhythmias (especially ectopic
ventricular beats and ventricular
bigemini).
Unstable arterial pressure.
Muscle
Masseter spasm if succinylcholine has
been used.
Generalized muscle rigidity.
Later signs
Hyperkalaemia.
Rapid increase in core body temperature.
Grossly elevated blood creatine
phosphokinase levels.
Grossly elevated blood myoglobin levels.
94
Dark-colored urine due to myoglobinuria.
Severe cardiac arrhythmias and cardiac
arrest.
Disseminated intravascular coagulation.
Heart rate monitoring
In general, continuous HR monitoring in the
ICU setting is obtained by bedside
electrocardiography (ECG). The use of ECG is
ubiquitous in the ICU and its application allows
for HR, rhythm, and waveform analysis and
monitoring. Often, changes in rhythm
accompany rate changes and, together, offer a
more comprehensive evaluation of the patient’s
underlying status. In most bedside monitoring
systems, respiratory rate and waveforms are
also measured and displayed on the
oscilloscope using the application of the ECG
electrodes. The selection of monitoring leads
should be guided by the published standards by
Drew and Funk (2006), according to the
patient’s condition and level of risk for
arrhythmia, myocardial ischemia, and/or
prolongation of repolarization waveforms (QT
interval monitoring) (also see Chapter 4).
The American Association of Critical Care
Nurses (2013) has advanced practice alerts
guiding alarm management, dysrhythmia
monitoring, and ST segment monitoring. For
general arrhythmia monitoring, lead V1 and
95
lead II are recommended for monitoring wide
QRS activity and atrial waveforms, respectively.
ST segment monitoring guidelines and selection
of leads depend on the bedside monitoring
system available. Generally, for patients at risk
of ST segment changes due to acute coronary
syndromes, the more leads that are available for
continuous monitoring, the greater is the
accuracy of detection of ST segment changes. If
the ST fingerprint is known, monitoring the
leads that have already shown changes during
ischemia is recommended. If these are not
available, and with monitoring systems in
which only two leads are available for
continuous ST segment monitoring, leads III
and V5 are recommended. The practice alerts
detail how to select and place leads accurately
and how to detect changes at the J point of the
QRS. Setting alarms to achieve notification
without overactivation may be difficult,
especially in patients with intermittent bundle
branch block (BBB), pacemakers, or frequent
ventricular arrhythmias. Table 2.4 represents
the settings currently recommended by
evidence. In most cases, clinical guidelines do
not specify the timing of monitoring, for
example, QT interval measurements when
continuous monitoring is unavailable. See
Chapter 4 for further information on ECG
monitoring.
96
Table 2.4 Published class I ECG monitoring
guidelines for heart rate and rhythm changes in
adults.
Adapted from Drew et al. (2004).
Parameter Recommendation Source
Heart rate
variations
ST segment 1–2 mm above and AACN (2009);
changes
below ST baseline at Drew et al. (2004)
during early 60 ms from J-point
phase of
acute
coronary
syndrome
(ACS)
Post cardiac ECG monitoring
Drew et al. (2004)
arrest
until an implantable
cardioverter
defibrillator (ICD) is
inserted or until
correction of cause
of arrest is made
and resolved
Unstable
coronary
syndromes
or newly
diagnosed
high-risk
Continous
Drew et al. (2004)
monitoring until
revascularization;
continue at least 24
h if arrhythmias or
ST changes occur
post intervention
97
Parameter Recommendation Source
coronary
lesions
Post cardiac Minimum 24–48 h Drew et al. (2004)
surgery
postop for all
patients; for those at
risk of atrial
fibrillation,
monitoring should
continue until
discharge
Post ICD or 12–24 h post
pacemaker implantation
Drew et al. (2004)
Patients
with Mobitz
II block,
complete
heart block,
or
new-onset
BBB in the
setting of
acute
myocardial
infarction
(AMI)
Monitor until
resolution of block
or definitive
treatment
Drew et al. (2004)
Acute heart
failure or
pulmonary
edema
Monitor until acute Drew et al. (2004)
heart failure and/or
hemodynamically
significant
98
Parameter Recommendation Source
arrhythmias have
been resolved for 24
h
Intensive
care
patients
Monitor until
weaned from
mechanical
ventilation and
hemodynamically
stable
Drew et al. (2004)
Conscious Continue until
sedation or patient is awake,
anesthesia alert, and
hemodynamically
stable
Drew et al. (2004)
QTc interval
(normal:
<0.46 in
women,
<0.45 in
men)
AACN (2008);
Drew et al. (2004)
(class I
monitoring
recommendations:
patients on
proarrhytmic
drugs known to
cause Torsades de
Pointes;
new-onset
bradycardia, OD
from potentially
proarrhythmic
agent, patients
with severe
QTc (corrected for
heart rate) should
be monitored in all
patients on
antidysrhythmics,
antibiotics,
antipsychotics, or
other drugs that
prolong QT interval;
severe bradycardia,
hypokalemia,
hypomagnesemia,
or drug overdose
(AACN, 2008, p. 1)
99
Parameter Recommendation Source
hypokalemia or
hypomagnesemia,
p. 14)
Class I recommendations are defined as those
in which cardiac monitoring is indicated in
most, if not all, participants in this group (p.
2722)
Blood pressure monitoring
BP measurement is very important in
monitoring critically ill patients, particularly
during shock states and management of
changing critical conditions. BP varies in a
diurnal pattern, with the highest pressures
generally evidenced between 6:00 a.m. and
12:00 a.m. and lowest during sleep (Ogedegbe
and Pickering, 2010). While critically ill adults
are frequently supine during measurement,
variation in measurement can be attributed to
arm position relative to torso location and
inappropriate cuff sizes selected for patients
(especially in obese or very thin individuals; see
Table 2.5). Rates of cuff deflation after inflation
should be 2–3 mmHg/s (Ogedegbe and
Pickering, 2010). An important surveillance
issue in BP measurement involves analysis of
systems and efficiency and accuracy of
measurements in individual patients. Many
factors
influencing
the
detection
and
surveillance of BP will be reviewed.
100
Table 2.5 Cuff sizes for appropriate BP
measurement in adults.
Adapted from Pickering et al. (2005).
Cuff
size
Arm
Recommended
circumference cuff size (cm)
(cm)
Small 22–26
adult
22 length; 12 width
Adult 27–34
30 length; 16 width
Large 35–44
adult
36 length; 16 width
Adult 45–52
thigh
42 length; 16 width
Oscillometric blood pressure
measurement
The measurement of BP has changed
considerably in recent years. The original
detection of Korotkoff sounds at the brachial
artery using a standard BP cuff, mercury
manometer, and stethoscope has gradually
been replaced in many critical care and
step-down units by automated oscillometric
measurement incorporated into bedside
monitoring systems. Oscillometric techniques
may raise concerns in measurement due to
many technical measurement and pulse
detection errors that arise in critically ill
patients. Tholl, Forstner, and Anlauf (2004)
101
identified issues with oscillometric device
accuracy, including calibration, vascular wall
elasticity, and size of the artery measured,
noting that atherosclerotic vascular changes
have a measurement effect on the oscillogram.
Ogedegbe and Pickering (2010) identified
measurement restrictions that have been
evaluated with arm measurement of BP. These
include the effects of posture, body positioning,
cuff size, and the occurrence of cuff-inflation
hypertension. If cuffs are not positioned
carefully, oscillometric systems may maintain
long inflation cycles, particularly in patients
with arrhythmias. As cuff inflation cycles are
prolonged, discomfort and bruising may
develop, especially when BPs are labile and
frequent measurements are conducted.
Aneroid measurement
Portable BP measurement may be conducted
intermittently
using
aneroid
sphygmomanometers and many of these
systems are wall-mounted although their use
has declined over the last decade. These devices
have largely replaced mercury manometers due
to safety concerns from mercury. Aneroid
sphygmomanometers have been generally
found to be reliable and accurate although they
are sensitive to mechanical damage and should
be calibrated annually (Tholl, Forstner, and
Anlauf, 2004). With reductions in the use of
mercury due to environmental concerns, Tholl,
102
Forstner, and Anlauf (2004) reviewed the
issues associated with accuracy using aneroid
and oscillometric techniques. These include
proper calibration, aneroid susceptibility to
inaccuracies following damage, technique of
cuff placement and measurement at the level of
the heart, arrhythmia influence on oscillometric
measurement, and proper deflation rates and
rest periods during repeated measurements
(Tholl, Forstner, and Anlauf, 2004).
Arterial pressure measurement
The accuracy of noninvasive blood pressure
(NIBP) compared with arterial invasive
monitoring has been studied in critically ill
overweight adults, finding both oscillometric
and auscultatory measurements to significantly
underestimate BP compared to direct arterial
measurement (Araghi, Bander, and Guzman,
2006). One serious inaccuracy of NIBP
concerns proper patient arm circumference
measurement and appropriate selection of cuff
size to obtain an accurate BP. Most unstable
patients will have invasive placement of arterial
catheters, generally in the radial or femoral
artery. In critically ill patients, continuous
arterial pressure monitoring allows for rapid
evaluation of the effects of therapies and
changing clinical condition. However, invasive
placement can be affected by many errors,
including dislodgement, positional waveforms,
requirements of appropriate line management
103
and tubing issues, as well as catheter dynamics.
Serious risks accompany the use of intraarterial
catheters, including bleeding, infection, and
phlebitis. Risks versus benefits of methods of
monitoring must be weighed in the selection
process. Evaluation of accuracy of methods
should be the responsibility of all team
members caring for the patient. Mignini,
Piacentini, and Dubin (2006) found minimal
bias and strong precision in mean BP
assessments comparing femoral and radial
arterial catheters in critically ill adults,
considering the values obtained as clinically
interchangeable. Although comparisons were
made during the first 5 min following insertion
in this study, the use of radial catheters is
common practice in most ICUs given increased
risk of infection with femoral line placements.
See Chapter 5 for further analysis of arterial
pressure monitoring.
Newer noninvasive methods are under
investigation for trending BP. Nowak et al.
(2011) evaluated the use of a finger cuff
technology (Nexfin®, Bmeye, The Netherlands)
to trend BP and HR in emergency department
patients. The Nexfin device uses a small finger
cuff with the capacity to display systolic
pressure, diastolic pressure, and MAP with
estimation of other hemodynamic parameters.
Nowak et al. (2011) compared the BP and HR
variables to those obtained using routine
cardiac and NIBP monitoring in 40 adult
104
patients using a convenience sample with data
collected every 15 min for 2 h. Both
Bland-Altman (mean bias = 0.87) and Pearson
correlation (0.83, p < 0.0001) suggested
acceptable agreement in the derived values.
Although further study is under way, newer
technologies that provide less invasiveness and
may be better tolerated by patients will
continually emerge. However, investigation of
these devices in patients with arrhythmias such
as atrial fibrillation is still needed.
Respiratory monitoring
Most respiratory rate monitoring is conducted
through plethysmography sensed by the chest
and abdominal movements of the electrodes of
the cardiac monitoring system. In many critical
care units, respiratory rates are also monitored
by ventilator systems designed to track pressure
and airflow during each respiratory cycle or by
monitoring end-tidal carbon dioxide levels.
Generally, patients with advanced respiratory
failure who require ventilatory support have
multiple methods available for tracking
respiratory rate and rhythm (see Chapter 3).
These are most important in evaluating trends
over time and allowing for the establishment of
alarms to alert practitioners to declining or
excessive respiratory rates or changing
rhythms, such as those associated with
Cheyne–Stokes
respiration.
Table
2.6
demonstrates common abnormal respiratory
105
patterns that are often associated
pulmonary pathologies in the ICU.
with
Table 2.6 Abnormal respiratory patterns
commonly seen in ICU patients.
From Baird and Bethel (2011). © Elsevier.
Assessing Respiratory Patterns
Type
Waveform
Eupnea
Bradypnea
Tachypnea
106
Hyperpnea
Apnea
107
Kussmaul
Cheyne-Stokes
Central
neurogenic
hyperventilation
108
Respiratory assessment and monitoring
includes active evaluation of patient effort and
depth of breathing, use of accessory muscles,
expansion and shape of the chest, ability to
speak during breathing effort, evidence of nasal
flaring, symmetrical chest expansion, and
auscultatory findings (Higginson and Jones,
2009). The use of pulse oximetry and
capnography enhances respiratory assessment,
supplements assessment findings, and guides
therapy, often saving costs by allowing for
reduction in arterial blood gas sampling during
periods of relative stability.
Capnography
Capnography is available in a number of
configurations and is widely used during
surgery and postanesthesia care. In the ICU,
capnography is generally used for intubated,
ventilated patients and most bedside
monitoring systems have modules for
continuous capnogram display. Widespread use
of
color-changing
CO2
detectors
is
recommended when a patient is first intubated
to ensure that an endotracheal tube is correctly
placed. Ccapnography provides waveform
displays of the entire ventilatory cycle and
continuous numeric display of the partial
109
pressure of end-tidal CO2 (Pet CO2).
Advantages of continuous capnography include
the ability to monitor all phases of inhalation
and exhalation, thus allowing for analysis of
changes in ventilation, perfusion, and dead
space trending (Cheifetz and Myers, 2007).
Indications for continuous capnography include
monitoring effects of conscious sedation,
endotracheal tube displacement, quality of
resuscitation efforts, and early findings in
patients with pulmonary emboli or low cardiac
output conditions (Johnson, Schweitzer, and
Ahrens, 2011). Monitoring and surveillance
require a strong understanding of the
relationship of phases of the ventilatory cycle to
the exhalation of CO2, the clinical condition of
the patient, and the ability to troubleshoot
alarm conditions. Capnogram waveform
analysis is covered in Chapter 3. No
randomized trials have shown definitively that
continuous monitoring of capnography in
intensive care patients alters outcomes
although capnography has been a standard of
care in intraoperative monitoring for decades
(Cheifetz and Myers, 2007).
Shock conditions in critically ill
adults
Shock conditions pose critical threats to life and
are regularly treated in critical care units
worldwide. Over the years, categories of shock
110
have been defined in a number of ways and the
evolution of shock management has changed as
more effective early assessment and treatments
have been studied. At the core of all forms of
shock, threats to tissue perfusion and
circulatory pathology generally lead to tissue
dysoxia (Antonelli et al., 2008). While
traditional definitions of shock have focused on
hypotension as a major sign, Antonelli and
colleagues (2007) published recommendations
guiding international shock management with
less emphasis on the presence of hypotension
and more on fluid responsiveness, markers of
regional and microcirculatory changes, and
hemodynamic monitoring, including advanced
monitoring
recommendations
for
the
management of critical care patients in shock
states (Antonelli et al., 2007). These include the
following:
The definition for shock is advanced as “a
life-threatening, generalized misdistribution of
blood flow resulting in failure to deliver and/or
utilize adequate amounts of oxygen leading to
tissue dysoxia” (p. 577) and not based on the
presence of hypotension.
Measurement of markers of impaired
oxygenation should supplement history and
physical exam data including markers of
inadequate perfusion such as reductions in
ScvO2 or SvO2, increased blood lactate, or
increased base deficit (p. 578).
111
Resuscitation efforts should target an MAP of
40 mmHg until bleeding is surgically
controlled; MAP of 90 mmHg for traumatic
brain injury; and for all other shock states, MAP
targets are over 65 mmHg (p. 578).
While preload measures alone should not be
used to predict fluid responsiveness in shock
states, low levels of static measures (central
venous pressure (CVP), right atrial pressure
(RAP), pulmonary artery occlusion pressure
(PAOP)) should trigger immediate fluid
resuscitation efforts in shock states and fluid
challenges are recommended to assess fluid
responsiveness. Based on literature support,
250 cc of crystalloid or colloid equivalent, or
straight leg raise maneuver should target a rise
in CVP of at least 2 mmHg, and dynamic
measures of fluid responsiveness are not
recommended, although it is acknowledged that
there may be advantages in selected patient
conditions (p. 580).
Routine measurement of cardiac output is not
recommended although ECG or measurement
in patients with ventricular failure and
persistent shock may be appropriate (p. 581).
Invasive BP measurement is recommended for
refractory shock but use of the pulmonary
artery catheter is not endorsed (p. 584).
Goal-directed therapy for septic shock is
supported within 6 h or less and use of
112
supranormal oxygen delivery systems is not
recommended.
Further published guidelines for sepsis
management and goal-directed therapy will be
covered in the following section on septic shock.
Important management of shock states requires
symptom and response analysis regardless of
type of monitoring devices employed.
Frequency of vital sign monitoring has
generally not been elucidated in the majority of
studies or guidelines and must be guided by
assessment findings in individual patients and
response to treatment.
Cardiogenic shock
Cardiogenic shock is associated with poor
peripheral perfusion secondary to primary
alterations in heart chamber filling or pumping
functions. This may develop as a result of
systolic or diastolic dysfunction or a
combination of these. Functional or structural
changes induced by trauma, pulmonary
embolism, pericarditis, cardiac tamponade, or
primary pulmonary conditions such as tension
pneumothorax may also result in cardiogenic
shock and death. Acute myocardial infarction,
particularly anterior wall involvement, is a
common
cause
of
cardiogenic
shock,
particularly if papillary muscles or extensive
myocardial damage is sustained.
113
The frequency of cardiogenic shock has
significantly declined over the past decade,
primarily attributed to improvement in
reperfusion
interventional
cardiology
techniques (Babaev et al., 2005). While overall
hospital mortality associated with cardiogenic
shock significantly declined from 1995 to 2004,
rates remained near 50% and application and
adherence to the published standards,
particularly early interventional strategies, were
stressed (Babaev et al., 2005). Published
guidelines for management of acute ST
elevation and non-ST elevation acute
myocardial infarction continue to evolve (Jneid
et al., 2013; O’Gara et al., 2013). These are
extensively reviewed by national experts
associated with the American Heart Association
and the American College of Cardiology
Foundation and employ evidence-based
practice guideline protocols advanced by these
organizations. Class I recommendations for
treatment of cardiogenic shock include
emergency revascularization (percutaneous
intervention or coronary artery bypass graft
(CABG)) or fibrolytic therapy in patients unable
to undergo interventional strategies and class II
recommendations including the use of
intraaortic balloon pump (IABP) (O’Gara et al.,
2013). In a 10-year study of outcomes
associated with cardiogenic shock, Babaev et al.
(2005) found that nearly 30% of 7356 patients
presented with cardiogenic shock while the
remaining 70% developed shock after hospital
114
arrival. Trends associated with improved
outcomes were identified with increasing
frequency
of
percutaneous
coronary
intervention (PCI), while CABG and IABP use
remained relatively stable over the study
period.
In the most recent updates on interventions for
acute
ST-segment
elevated
myocardial
infarction (STEMI), the strongest evidence
included early recognition of acute myocardial
infarction, with a 12-lead measurement and
transmittal by emergency medical personnel,
expedited hospital intervention (door to balloon
times of 90 min or less; door to thrombolytic
intervention in areas without rapid access to
interventional cardiology procedures of 30 min
or less), early pharmacologic interventions to
reduce cardiac workload and platelet
aggregation, oxygen administration, and pain
management (O’Gara et al., 2013). While most
hospitals have developed extensive emergency
medical system (EMS) and emergency
department (ED) protocols that require
coordination
and
intervention
across
disciplinary units within the hospital, many
geographical areas find implementation of
published guidelines difficult due to remote
access or EMSs that are primarily staffed by
volunteers. Collaboration across disciplines is
critical to ensure best outcomes for patients at
risk of cardiogenic shock and to decrease
115
mortality and morbidity associated with cardiac
emergencies.
Anaphylactic shock
Anaphylaxis
develops
following
a
hypersensitivity reaction to an antigen,
mediated by immunoglobulin E. Medication,
foods, insect bites or stings, and radiocontrast
dyes are all common antigens that can affect
humans (Sheikh, 2013; Soar and Unsworth,
2009). In anaphylactic shock, widespread
vasodilation
and
increased
capillary
permeability are triggered, with fatality ranging
from 1:1000 exposures to food products to
1:100 for medication or insect venom
(Kirkbright and Brown, 2012).
Clinical guidelines for the treatment of
anaphylaxis have been published (Soar et al.,
2008). These include a focus on assessment of
airway, breathing, circulation, disabaility, and
exposure
(ABCDE),
administration
of
intramuscular adrenalin, and evaluation and
protection of patients including long-term
management strategies for self-administration
of adrenalin (Soar et al., 2008). Figure 2.1
demonstrates the anaphylaxis algorithm in
these guidelines. Treatment for anaphylaxis
involves administration of adrenalin 1:1000,
dosed at 0.01 mg/kg IM with a maximum initial
dose of 0.5 mg (Kirkbright and Brown, 2012).
116
Figure 2.1 Anaphylaxis algorithm.
117
Reprinted with permission from The exact
terminology for reprinting states that the credit
should read as follows Reprinted with permission
from The Royal Australian College of General
Practitioners from Kirkbright, SJ, Brown, SGA.
Anaphylaxis–Recognition and management. AFP
2012; 41:366–70. © The Royal Australian College
of General Practitioners/Australian Family
Physician.
Most patients will receive intravenous (IV)
therapy with normal saline. Patients should be
kept recumbent to enhance venous return and
observed for complications as recurrent
symptoms may occur in association with
late-phase reactions (Thompson, 2012).
Patients with known allergens and prior
anaphylaxis should be instructed to carry
adrenalin autoinjectors for rapid treatment
following future exposure (Soar and Unsworth,
2009). Education is an important aspect of care
following anaphylaxis. Despite the widespread
use of adrenalin for treatment, no randomized
controlled trials have demonstrated its
effectiveness; due to its long use and clinical
effectiveness in treatment, a Cochrane review
noted that ethical issues and the unexpected
development of anaphylaxis will continue to
restrict the use of controlled trials guiding
anaphylactic management (Sheikh et al., 2012).
Frequency of monitoring remains understudied
but generally minimal monitoring includes
ECG, pulse oximetry, and all vital signs until
the risk of recurrent anaphylaxis has passed
118
(Soar and Unsworth, 2009). All areas of
hospital care should be equipped to treat
anaphylaxis.
Hypovolemic shock
Burns, traumatic injuries, and hemorrhagic
shock are commonly treated in the ICU but may
also
develop
secondary
to
operative
complications. Over the past decade, more
aggressive
monitoring
and
assessment
techniques have been identified with the
realization that hypotension, skin turgor
changes, and capillary refill testing are often
nonspecific or late signs in the development of
shock conditions (Thompson, 2012). Methods
to monitor fluid responsiveness are covered in
Chapter 5. Generally, hypovolemic shock states
develop in rapidly sequential patterns when
hemorrhage and burns occur (see also Chapter
10). It is important to assess preload changes
and determine responsiveness to fluid
administration, and early detection of the
source of the shock is critical to management.
Pacagnella et al. (2013) conducted a systematic
review on indicators for severity of hypovolemic
shock and found considerable variation among
etiologies. The use of the shock index (SI) was
found to be a helpful tool in assessing
cardiovascular effects of shock. The SI is
calculated as the ratio between the HR and
systolic blood pressure (SBP) and allows for a
rapid analysis of cardiovascular response to
119
fluid loss. Clear guidelines for complex patient
management, including management of
patients with concurrent heart failure and
trauma, remain difficult and require careful
assessment and evaluation.
Sepsis syndromes
Sepsis, as an antecedent of severe sepsis, septic
shock, and multisystem organ dysfunction
syndrome (MODS), is a complex process that is
defined by the presence of systemic
inflammatory responses to the presence of an
infection and represents the tenth leading cause
of death in the United States (CDC, 2010). Data
show that sepsis affects more than 1.1 million
persons and carries mortality rates as high as
59% (Angus et al., 2001; Legrand et al., 2012;
Zuber et al., 2012). Rates of sepsis have
increased despite the advancement in treatment
options although increasing awareness and
published guidelines have improved efforts and
raised awareness for reducing this condition. It
is imperative to recognize sepsis in its early
stages in order to improve outcomes (Dellinger
et al., 2013). In accordance, The Surviving
Sepsis Campaign was instituted by health-care
organizations to define sepsis and its sequelae,
and to set forth monitoring and therapy
guidelines to improve early recognition and
treatment for patients at risk for sepsis
(Dellinger et al., 2008). These guidelines
focused on initial management, identification,
120
and treatment of the infectious source
(Dellinger et al., 2008). Initial management
recommendations
include
management
strategies for the first 6 h, effective methods of
diagnosis, antibiotic treatment, source of the
infection, and infection control. Helpful tables
summarize hemodynamic support, fluid
management, and the use of steroids and other
medications. These guidelines have been
incorporated into most orientation and
educational programs for the preparation of
critical care practitioners. Key management
strategies include identifying the source of the
infection and eliminating it, containing the
systemic response, supporting macrocirculatory
needs and hemodynamics, and overall support
of failing systems. Assessment findings in early
sepsis may be seen in Table 2.7.
Table 2.7 Assessment findings in sepsis.
From Baird and Bethel (2011, p. 925). ©
Elsevier.
Clinical
indicator
Cause
Cardiovascular
Increased HR
(> 100 heats/
min)
Sympathetic/autonomic
nervous system (SANS)
stimulation
Decreased BP
(<90 mm Hg
Vasodilation
121
Clinical
indicator
Cause
systolic, MAP
<65 mm Hg)
CO >7 L/min;
Cl >4 L/min/
Hyperdynamic state
secondary to SANS
stimulation
m2, CVP < 8
mm Hg
Svo2 >80%
Decreased utilization of
oxygen by cells
PAWP usually
<6 mm Hg
Venous dilation; decreased
preload
SVR < 900
Vasodilation
dynes/sec/cm
–5
Strong,
bounding
peripheral
pulses
Hyperdynamic
cardiovascular system
(Keeping in mind that
patients with preexisting
cardiomyopathy will have
minimal elevation in cardiac
output and drop in SVR)
Respiratory
Tachypnea (>20
breaths/min)
and
hyperventilation
Metabolic acidosis which
leads to decreases in
cerebrospinal fluid pH that
stimulate the central
respiratory center
122
Clinical
indicator
Cause
Crackles
Interstitial edema occurring
with increased vascular
permeability
Paco2 <35 mm
Hg
Tachypnea and
hyperventilation
Dyspnea
Increased respiratory muscle
work
Renal
Decreased urine Decreased renal perfusion
output (<0.5
ml/kg/hr)
Increased
specific gravity
(1.025–1.035)
Decreased glomerular
filtration rate
Cutaneous
Flushed and
warm skin
Vasodilation
Metabolic
Increasing body
temperature
(usually
>38.3°C
[100.9°F])
Increased metabolic activity;
release of pyrogens
secondary to invading
microorganisms; release of
interleukin-1 by
macrophages
123
Clinical
indicator
Cause
pH < 7.35
Metabolic acidosis occurring
Lactic acid >2.5 with accumulation of lactic
acid
↑ Blood sugar or Release of glucagon; insulin
resistance
at times
profound
hypoglycemia
Neurologic
Changes in LOC Decreased cerebral perfusion
and brain hypoxia
Fluid
↑ Fluid
retention
↑ ADH, ↑ aldosterone
ADH, Antidiuretic hormone; beats/min, beats
per minute; BP, Blood pressure; CO, cardiac
output; CI, cardiac index; HR, heart rate; LOC,
level of consciousness; PAWP, pulmonary
artery wedge pressure; SVR, systemic vascular
resistance.
Monitoring for tissue hypoperfusion is critical.
Jones and Puskarich (2011) identifed global
variables that reflect tissue hypoperfusion.
These include hypotension, tachycardia, low
cardiac output, mottled skin, delayed capillary
refill, altered mental state, hyperlactemia, and
low mixed venous and central oxygen
saturation. Giuliano and Kleinpell (2005)
124
surveyed experienced and/or certified critical
care nurses and physicians in attendance at two
major conferences in 2003 to determine the
clinical practice of continuous monitoring for
patients with sepsis. Over 600 participants
identified invasive BP monitoring, pulse
oximetry, cardiac monitoring, and pulmonary
artery pressure monitoring as the top
continuous monitoring parameters for this
patient population. While options for
hemodynamic management continue to evolve,
sepsis monitoring continues to be complex and
the essential role of early intervention and
goal-directed therapy has improved outcomes
in this highly lethal shock condition. The critical
role of a multidisciplinary approach to care is
essential to positive outcomes.
While hemodynamic monitoring in sepsis
remains controversial, it may augment trends
in a patient’s condition and tolerance of rapidly
changing
hemodynamic
treatment
and
management effects. CVP changes remain part
of published sepsis guidelines and additional
techniques are under investigation to move
toward less invasive and more continuous
measurement of cardiac output and stroke
volume (see Chapter 5).
SIRS, sepsis, and septic shock
Systemic inflammatory response syndrome
(SIRS), the prequel to sepsis, is an
overwhelming, multisystem response to injury
125
or infection. This response was initially defined
by the presence of two or more of four clinical
indicators including temperature (>38 °C or
<36 °C); HR (>90 beats/min); respiratory
changes (>20 breaths/min or PaCo2 < 32
mmHg); and white blood cell elevations (>12 ×
109/l or <4 × 109/l, or >10% bands)
(ACCP-SCCM Consensus Conference, 1992;
Dellinger et al., 2013). SIRS in the presence of a
presumed or documented infection denotes
sepsis (Table 2.8), while severe sepsis indicates
the presence of sepsis-induced tissue
hypoperfusion (altered mental status, shock,
oliguria, or elevated lactic acid level) or acute
organ dysfunction. Septic shock is defined as
persistent sepsis-induced hypotension (SBP <
90 mmHg, MAP < 70 mmHg, or SBP drop of
>40 mmHg from baseline), despite adequate
volume resuscitation (Dellinger et al., 2008).
The goal is to implement care bundles within 3
and 6 h of symptom presentation to prevent
shock development. In the latest international
guidelines, recommendations are for serum
lactate, blood culture administration prior to
antibiotics, and administration of 30 ml/kg
crystalloids for hypotension or serum lactate ≥4
mmol/l (Dellinger et al., 2013). Within 6 h,
recommendations include vasopressor support
for hypotension unresponsive to fluid
administration, and implementation of central
venous pressure monitoring with CV oxygen
saturation and reassessment of lactate levels, if
126
initially
elevated.
Targeted
results
of
resuscitation efforts within 6 h are to attain a
CVP of 8–12 mmHg, mean arterial pressure
≥65 mmHg, ScvO2 ≥ 70% or SvO2 ≥ 65% and
normalization of serum lactate in those with
prior elevation (Dellinger et al., 2013, p. 587).
Table 2.8 Risk factors for sepsis.
Adapted from Balk (2000); Esper and Martin
(2009); Kleinpell (2003); Legrand et al. (2012);
Picard et al. (2006).
Age extremes (<1 year and >65 years)
Diabetes
Cancer
Chronic kidney disease
End-stage liver disease
Malnutrition
Alcoholism
Tobacco use
Hypothermia
Mechanical ventilation
Invasive or surgical procedures
Presence of drug-resistant organisms
Prior use of broad-spectrum antibiotics
Major trauma
Major burns
127
Age extremes (<1 year and >65 years)
Presence of invasive lines/tubes
Urinary catheters
Endotracheal tubes
Central venous access devices
Immunocompromised
HIV/AIDS
Neutropenia
Immunosuppressives
Chemotherapeutic agents
Organ transplantation
Morbidity and mortality due to severe sepsis
and septic shock develops from dysfunctional or
failed end-organ systems such as the kidneys,
lungs, heart, brain, and liver. See also Sepsis in
the Immunocompromised Host (Chapter 11).
Monitoring and treatment priorities in sepsis
syndromes
Priorities for care of patients admitted to
critical care units include the following:
Identify patients at high risk for sepsis.
Stabilize patients with severe sepsis or septic
shock.
128
Administer antimicrobial agents to rapidly
eradicate microorganisms following
cultures.
Treat infectious foci, such as drainage of
abscesses/purulent collections or surgical
repair of enteric injuries.
Monitor acid–base, oxygenation, and
hemodynamics in order to optimize oxygen
delivery to tissues and organs.
Sepsis diagnosis
The diagnosis of sepsis is based on the
assessment of risk factors and clinical signs and
symptoms (Table 2.9). An accurate history and
physical exam are the first steps in assessing
patients for risk factors and signs and
symptoms of sepsis. This may be difficult if
patients are confused, medicated, or have
cognitive impairments that preclude accurate
history taking. Use of family, significant others,
emergency personnel, and medical records can
aid in obtaining a complete history (Nduka and
Parrillo, 2011). Signs of early sepsis, such as
change in vital signs, restlessness, lethargy, and
confusion are often subtle or attributed to other
etiologies.
Table 2.9 Sepsis diagnostic criteria.
Adapted from Cunneen and Cartwright (2004);
Levy et al. (2003).
129
General
Hypothermia (core temperature <36 °C)
Fever (core temperature >38 °C)
Tachycardia (>90 beats/min)
Tachypnea (respiratory rate (RR) > 20
breaths/min)
Confusion or altered mental status
Hyperglycemia (>120 g/dl in nondiabetics)
Positive fluid balance (>20 ml/kg over 24 h)
Hematologic/inflammatory
Leukocytosis (WBC > 12 000)
Leukopenia (WBC < 4 000)
Immature neutrophils (bands > 10%)
Thrombocytopenia (platelets < 100 000/µl)
Hemodynamics
Hypotension (MAP < 70 mmHg, or SBP < 90
mmHg, or SBP decrease of >40 mmHg from
baseline)
Cardiac index >3.5 l/min/m2
SvO2 > 70%
Stroke volume variation (>15%)
Organ dysfunction
130
General
Acute kidney injury (creatinine rise >0.5 mg/
dl or urine output <0.5 ml/kg/h ideal body
weight (IBW))
Arterial hypoxemia (PaO2/FiO2 < 300)
Coagulopathy (international normalized ratio
(INR) > 1.5 or partial thromboplastin time
(PTT) > 60 s)
Illeus
Hyperbilirubinemia (total bilirubin >4 g/dl)
A-a gradient >20 mmHg
Tissue perfusion
Lactic acidosis (>1 mmol/l)
Anion gap >20
Mottled extremities or decreased capillary
refill
Body temperature
Abnormal body temperature is often the first
indicator that a patient is septic. Normal body
temperature is 37 °C (+/−1 °C), but this can
vary +/−0.5–1 °C based on circadian rhythm
and menstrual cycle. Strenuous exercise can
increase core temperature by up to 3 °C.
Environmental factors such as specialty beds,
room temperature, therapeutic interventions
131
(drugs, dialysis, and cardiopulmonary bypass),
and
endocrine
disorders
(hypoor
hyperthyroidism)
can
also
alter
core
temperatures
(O’Grady
et al., 2008).
Hyperthermia in response to infection is
defined as a core temperature greater than
either 38.3 or 38 °C in neutropenic patients.
Almost half of critical care patients have at least
one febrile episode and these episodes are more
common in medical patients. Hypothermia is
defined as a body temperature below 36 °C and
may be noted more commonly in surgical
patients, the elderly, or in patients with hepatic
failure, heart failure, open abdominal wounds,
or major burns. Mortality has been associated
with both hyper- and hypothermia, but occurs
more frequently in hypothermic patients
(Laupland et al., 2012; O’Grady et al., 2008).
The presence of hyper- or hypothermia should
trigger investigation for cause, especially if
signs of SIRS, organ dysfunction, or
hypotension are present, but consideration
should be given to the accuracy of temperature
measurements. The American College of
Critical Care Medicine and the Infectious
Diseases Society of America have published
guidelines ranking pulmonary artery, urinary
bladder catheter, and esophageal and rectal
probes as more accurate than infrared ear,
temporal artery, oral and axillary thermometers
(O’Grady et al., 2008).
132
Cultures
Blood cultures should be obtained when there
are clinical signs of infection or sepsis.
Approximately 50% of blood cultures are
negative in septic patients. Therefore, care
should be taken in collecting two sets prior to
initiation of antibiotics, transporting the
samples to the laboratory, and meticulously
preparing the skin with 2% alcoholic
chlorhexidine or 1–2% tincture of iodine. A
volume of at least 10 ml/bottle should be
drawn, with one being drawn from any vascular
access device in place for more than 48 h
(Dellinger et al., 2008; O’Grady et al., 2008).
Common microorganisms found in cultures
guide practitioners in selecting empiric
antimicrobial prescriptions.
Intravascular catheters
The risk of bloodstream infections is highest
with noncuffed temporary venous hemodialysis
catheters, followed by central lines, then
peripherally inserted central venous lines and
implanted ports (Mermel et al., 2009). It is
recommended that short-term catheters be
removed and cultured if line sepsis is
considered. Cultures of catheter insertion sites
are notoriously nonspecific and carry a high
frequency of false positive results, leading to
unnecessary device removal. Diagnosis of a
catheter-related bloodstream infection is based
on positive cultures of identical microorganisms
133
from both intracutaneous (5–7 cm of
intradermal catheter section) and blood
cultures. Central catheters in patients who have
fever alone (no signs of SIRS or sepsis) should
not routinely be removed (O’Grady et al.,
2008).
Other infectious complications in
critically ill adults
Pulmonary infections
Hospital-associated pneumonia (HAP) is the
second most common nosocomial infection and
carries a mortality rate of up to 50%, with the
majority
of
ICU
patients
having
ventilator-associated pneumonia (VAP) (ATS/
IDSA, 2005; Dellit et al., 2008; Labeau et al.,
2008). VAP carries a mortality rate of 24–76%
(Dellit et al., 2008; Kollef et al., 2008). Classic
signs and symptoms of pneumonia include
fever, cough, leukocytosis, and dyspnea
(Andrews, 2012). In ICU patients with
endotracheal tubes, fever and increased sputum
production (or changes in pulmonary secretion
characteristics) are often the first indicators of
pneumonia (O’Grady et al., 2008). Sputum
sampling for culture and sensitivity can be
accomplished via expectoration, tracheal
suctioning, or bronchial alveolar lavage (with or
without bronchoscopy), with the goal of
obtaining a lower respiratory tract sample
134
without
oral
secretion
contamination.
Bronchoscopy is particularly helpful in
obtaining
adequate
samples
with
Mycobacterium
(acid-fast
bacilli),
Pneumocystis jiroveci (or pneumocystis
pneumonia (PCP), Aspergillus and other fungi,
Legionella species, and cytomegalovirus
(CMV).
Urinary
antigen
testing
for
Streptococcus pneumoniae and Legionella
(serogroup 1) is available and provides rapid
turnaround times for results. Direct fluorescent
antibody staining for influenza A and B should
be performed on patients with respiratory
symptoms during the fall and into the spring
months (Mandell et al., 2007).
A chest radiograph should be obtained to assess
for pulmonary infiltrates. Although the
anteroposterior (AP portable) method is safer
for patients, its reliability may be limited due to
patient positioning, disease process, and
equipment. If there is difficulty in interpreting
the portable film, high-resolution computerized
tomography can aid in the diagnosis of complex
pleural effusions, cavitations, and posterior and
inferior lung disorders (O’Grady et al., 2008). A
diagnostic thoracentesis should be performed
to obtain cultures in patients with pleural
effusions associated with adjacent infiltrates to
rule out aerobic or anaerobic empyemas
(Mandell et al., 2007).
135
Urinary tract infections
Bacteriuria due to bladder catheterization is the
most common health-care-associated infection
in the world. The conventional signs and
symptoms of urinary tract infection (UTI)
include dysuria, hesitancy, frequency, chills,
hematuria, malaise, new onset fever, and flank
or pelvic pain but are often absent in ICU
patients. Bacteriuria and candiduria as the
cause of bacteremia and sepsis occur in less
than 15% of patients. Patients with tract
obstructions (calculi, tumors), hydronephrosis,
renal transplantation, tract manipulation
procedures or surgery, neutropenia, and who
reside in long-term care facilities have the
highest rates of UTI-associated bacteremia.
Mortality from bacteremic UTI is cited at
approximately 13% (Hooton et al., 2010;
O’Grady et al., 2008).
Diagnosis of catheter-associated UTI (CAUTI)
is based on the presence of bacteria or fungus,
at concentrations over 103 colony-forming units
(CFU)/ml in patients with signs and symptoms
of UTI, and in patients without signs or
symptoms or who are wearing a condom
catheter, concentrations over 105 CFU/ml. The
presence of pyuria (WBC > 105/ml) in a urine
sample is indicative of UTI only in
community-acquired infections and should not
be used in diagnosis. Additionally, cloudy or
foul-smelling urine in catheterized patients is
136
not a sensitive indicator of UTI (Hooton et al.,
2010; O’Grady et al., 2008). Prevention of
CAUTI should be targeted and indwelling
catheters removed at the earliest time of
stabilization of critically ill septic patients.
In summary, the care of patients with suspected
shock syndromes has become increasingly
protocolized and systematic. Further outcome
studies are warranted to decipher best practices
across a range of patient conditions and
attributes.
Monitoring during transport
Maintaining the same level of diligent
surveillance during transport is often
challenging to ICU staff. Day (2010) reviewed
the goals of safe transport, including the
maintenance of ICU standards of care and
monitoring during transport, ensuring patient
stability and avoiding complications while
achieving the goals of obtaining quality
diagnostic study or intervention. In general, if a
patient is unstable, transporting should be
avoided unless the diagnostic study or
intervention is lifesaving. Drew et al. (2004)
also addressed the imperative of continuous
cardiac monitoring during transport equivalent
to bedside monitoring in the ECG-monitoring
practice standards.
Portable monitoring devices in many models of
ICU bedside systems now allow for quick
137
transport readiness. However, transport
remains a risky endeavor for patients who are
on life-support equipment and often requires
the expertise of a cadre of critical care staff for
successful monitoring and safety during
transport.
Conclusion
Surveillance of vital signs is critical to care
management in intensive care settings,
particularly during treatment of shock
conditions. While vital sign measurement and
analysis is part of continual monitoring
practices in the ICU, few studies have validated
the most effective methods or frequency of
monitoring. Given that considerable time is
spent by nurses on equipment management,
trending, and managing interventions based on
vital signs, further research is needed to
identify practices that are efficient and enhance
good patient outcomes. Rapid treatment and
complex management of shock states is critical
to good outcomes. While considerable research
on conditions such as sepsis and targeted
temperature management has emerged in the
past decade, further studies are needed,
including basic examination of effective BP
measurement using variable cuff types, and
effectiveness and efficiency studies on all vital
measurements. Especially needed are studies
that examine measurement techniques that
allow optimal discernment of vital changes and
138
measurement systems that provide optimal
analysis, enhance safety, and are well tolerated
by critically ill patients. The use of technical
equipment varies considerably in ICU settings.
Nursing surveillance and management of these
systems is critical to ensuring accurate data that
capably guide therapy and care of critically ill
adults.
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153
Chapter 3
Monitoring for respiratory
dysfunction
Alexander P. Johnson1 and Jennifer Abraham2
1
Cadence Health, Central DuPage Hospital,
Winfield, IL., USA
2
Advocate BroMenn Medical Center, Normal,
IL., USA
Respiratory dysfunction and subsequent failure
is a common reason for admittance to the
critical care unit. While underlying lung disease
may not be the primary cause of respiratory
failure, all systems are highly dependent on
adequate ventilation. Septic shock, trauma,
acidosis, and cardiovascular emergencies can
all result in respiratory failure. Underlying
comorbidities including obesity can complicate
pulmonary support, and should be considered.
The clinician’s ability to monitor effectively and
treat the patient urgently in respiratory failure
is critical to the patient’s outcome.
This chapter focuses on primary causes of
respiratory dysfunction in the critical care unit,
strategies for monitoring and treatment, and an
overview of ventilatory support. Key elements
of monitoring and treatment will be
154
highlighted, as well as supporting evidence and
clinical pearls that will hopefully make the
content easy to use at the bedside.
Acid-base disturbances & anion
gap
A systematic approach to arterial blood gas
(ABG) analysis can help accurately and rapidly
identify the underlying cause of an acid–base
disorder. The four following primary categories
of
abnormal
blood
gas
changes
compartmentalize blood gas interpretation in
order to facilitate triage and treatment of
critical care patients.
Metabolic acidosis
Disorders causing metabolic acidosis can be
categorized into two groups: (1) anion gap
metabolic acidosis and (2) non-anion gap
acidosis. This can help clinicians quickly
differentiate the underlying cause of the
acidosis. An increased anion gap is generally
associated with increased acid production or
administration, and nonanion gap acidosis is
associated with increased bicarbonate loss or
loss of bicarbonate precursors. The anion gap is
the expected difference between measured
serum cations and anions under normal
conditions. The normal anion gap is 7–16, and
the formula for the gap is as follows:
155
Be aware that some clinicians omit potassium
from the calculation due to its minimal
influence on the equation.
Clinical pearls
Many venous chemistry panels list
bicarbonate as “CO2.”
Identification of the underlying cause can be
further simplified with respect to the fact that
three main types of metabolic acidosis are
generally seen in intensive care unit (ICU)
patients:
Renal acidosis
Diabetic ketoacidosis
Lactic acidosis
The most common of the three causes is
lactic acidosis (type-A form). Type-A lactic
acidosis is a global indicator of tissue hypoxia
and elevated levels should prompt
investigation regarding the underlying cause
including, but not limited to, bleeding, low
cardiac output (e.g., heart failure), or
hypovolemia. Common causes of metabolic
acidosis are reviewed in Table 3.1 and a
diagnostic algorithm for metabolic acidosis is
provided in Figure 3.1.
156
Table 3.1 Causes of metabolic acidosis.
Anion gap acidosis Nonanion gap
acidosis
Methanol
intoxication
GI losses (i.e.,
diarrhea, fistulas,
drains)
Uremia (chronic
renal failure)
Renal tubular
acidosis (RTA)
Lactic acidosis
Total parenteral
nutrition fluids
Ethylene glycol (i.e.,
antifreeze solution)
Carbonic anhydrase
inhibitors
Paraldehyde
intoxication
Ammonium chloride
ingestion
“Aspirin” (salicylic
acid)
Ketoacidosis
Anion gap acidosis clinical pearl: The
acronym MULEPAK may help practitioners
remember the types of anion gap metabolic
acidosis. Rule these out, and the nonanion
gap types are the likely cause.
157
Figure 3.1 Diagnostic algorithm for
metabolic acidosis.
From Ferri (2004). © Elsevier.
158
Clinical pearls
Do not completely rule out metabolic acidosis
based solely on bicarbonate levels within the
“normal” reference range (22–26 mEq/l). A
seemingly normal bicarbonate level may be
low relative to the patient’s baseline (e.g., an
end-stage chronic obstructive pulmonary
disease (COPD) patient with chronically high
serum bicarbonate).
Clinical pearls
For every 10 mEq decrease in bicarbonate,
the pH will decrease by 0.15.
Metabolic alkalosis
Metabolic alkalosis is generally less dangerous
than metabolic acidosis. A few common causes
of metabolic alkalosis exist:
Excessive gastrointestinal (GI) losses (i.e.,
increased gastric output, vomiting)
Diuretic infusions (e.g., continuous lasix
infusion)
Excessive administration of NaHCO3
159
See Figure 3.2 for a more detailed diagnostic
algorithm for metabolic alkalosis.
Figure 3.2 Diagnostic algorithm for metabolic
alkalosis.
From Ferri (2004). © Elsevier.
Respiratory acidosis
Carbon dioxide (CO2), a by-product of cellular
metabolism, accumulates in the blood due to
hypoventilation secondary to a decrease in
minute ventilation. Initial interventions to treat
respiratory acidosis include supporting airway
and breathing. This may include airway
maneuvers such as a head tilt and chin lift, jaw
160
thrust, or airway devices such as oral and
nasopharyngeal airways. Ambu bag-valve mask,
bilevel positive airway pressure (BiPAP), or
mechanical ventilation may be required to
support
ventilation,
increase
minute
ventilation, and decrease PaCO2. Reversal of
sedative or narcotic agents must also be
considered, as well as underlying pathologies
such as stroke, seizure, atelectasis, or effects
from drug overdose when strategizing how to
increase the patient’s respiratory rate or depth
in order to resolve the acidosis.See Figure 3.3
for a more detailed diagnostic algorithm for
respiratory acidosis.
Clinical pearls
For every 10 mEq increase in bicarbonate,
the pH will increase by 0.15.
Figure 3.3 Diagnostic
respiratory acidosis.
161
algorithm
for
From Ferri (2004). © Elsevier.
Respiratory alkalosis
Respiratory alkalosis generally occurs in
association with two main clinical scenarios:
Overventilation due to pain, fear, or
other anxiety-provoking stimuli.
Treatment efforts should focus on removing
offending stimuli or administering
analgesics or anxiolytics as needed.
Decreasing mandatory rate and/or tidal
volume should be considered in
mechanically ventilated patients.
Compensatory mechanisms. If the
respiratory alkalosis exists as a
compensatory mechanism for metabolic
acidosis, treatment of the underlying cause
must be addressed as soon as possible (e.g.,
diabetic ketoacidosis (DKA). If the patient
exhausts the ability to hyperventilate,
decompensation or even death may occur.
Clinical pearls
For every 10 mmHg decrease in PaCO2,
the pH will increase by 0.08.
See Figure 3.4 for a more detailed diagnostic
algorithm for respiratory alkalosis.
162
Figure 3.4 Diagnostic
respiratory alkalosis.
algorithm
for
From Ferri (2004). © Elsevier.
Mixed acid–base disorders
When one of the four earlier mentioned
acid–base disorders is superimposed upon the
other, this is generally referred to as a “mixed”
acid–base disorder. Determining whether or
not a mixed disorder exists begins with the fact
that for every 10 points the CO2 or HCO3
increases or decreases, the pH should change
proportionately. If not, a mixed disorder is
present.
Oxygenation
Estimation of the PaO2
The predictability of the oxyhemoglobin
dissociation curve can allow clinicians to
estimate the PaO2 based on the patient’s
163
existing PaO2 and FiO2. Provided hemoglobin’s
affinity for O2 is normal:
If the SaO2 is 99%, then the PaO2 will be 100
mm.
If the SaO2 is 95%, then the PaO2 will be 80
mm.
If the SaO2 is 90%, then the PaO2 will be 60
mm.
If the SaO2 is 85%, then the PaO2 will be 50
mm.
Clinical Pearls
The “rule of 5 s.” The FiO2 multiplied by 5
should be approximately the value that the
PaO2 should be (caution: this estimation is
not exact). For example:
A–a Gradient
Calculating the alveolar–arterial oxygen (A–a)
gradient provides an indication of how well
alveolar oxygen moves into the arterial blood,
and whether gas exchange is normal or altered.
The A–a gradient differentiates hypoxemic
disturbances due to either hypoventilation or
low inspired PaO2 (which have normal A–a
gradients) from other causes such as shunting
164
or V/Q mismatch (which have increased A–a
gradients). While a decreased A–a gradient is
the objective, “normal” values vary with age,
FiO2 concentration, and barometric pressure.
Generally, the gradient should be less than
10–15 mmHg on room air. As a general rule, a 3
mmHg increase is expected for every decade of
life after the age of 30. An estimation of normal
can be gauged by utilization of the following
formula:
A–a gradients will be 5–25 mmHg for an FiO2
= 21% and should be less than 150 mmHg for
an FiO2 of 100%. Most ABG analyzers calculate
the A–a gradient. A more exact estimation can
be made using the alveolar gas equation,
although this would be cumbersome to
calculate at the bedside.
PaO2/FiO2 (P/F) ratio
An easier, less complex calculation of
pulmonary shunting is the P/F ratio. The ratio
is simply the PaO2 obtained from the ABG
divided by the FiO2 concentration. A normal
value is considered anything greater than 250
Torr, and the shunt worsens as the P/F ratio
decreases. For example:
165
Values less than 250 are considered abnormal
and require investigation regarding the
underlying cause. P/F ratios less than 200 are
associated with severe shunting such as in adult
respiratory distress syndrome (ARDS). The
2008 Surviving Sepsis Campaign International
Guidelines for Severe Sepsis and Septic Shock
classify pulmonary organ dysfunction as acute
lung injury with P/F ratio less than 250 in the
absence of pneumonia as the infection source
and less than 200 in the presence of pneumonia
as the sepsis source (Dellinger et al., 2008).
Acute respiratory failure
A systematic approach to acute respiratory
failure facilitates identifying the underlying
cause and subsequent treatment. Generally,
acute respiratory failure can be classified into
three kinds:
Hypercapnic (CO2 > 45) due to the
inability of accessory muscles to provide
adequate minute ventilation (e.g., narcotic
overdose or inability to compensate for
metabolic acidosis any longer).
Hypoxemic (PaO2 < 60 mmHg) (e.g.,
severe shunting like pneumonia or ARDS).
Passive delivery of O2 is insufficient to
improve oxygenation and patient needs
positive end-expiratory pressure (PEEP) or
other pressure support delivery.
166
PEEP titration can help reduce FiO2 levels
(goal < 60%) and avoid oxygen toxicity.
Other causes of hypoxia, such as low cardiac
output (circulatory hypoxia) and anemia
(anemic hypoxia), should be considered.
Inability to maintain an airway and/
or manage secretions (e.g., altered
mental status due to combinations of
hypercapnia and hypoxemia).This may
occur with profound respiratory muscle
weakness due to altered mental status,
excessive sedation, or drug overdose states.
Clinical Pearls
Restlessness can be an early sign of hypoxia.
Take caution not to sedate the patient or give
anxiolytics to the patient with impending
respiratory failure.
Clinical Pearls
Do not be afraid to give 100% oxygen to
deteriorating patients out of fear that they
are CO2 retainers. In the emergent setting,
always give enough oxygen to keep SaO2 >
90%. Moving forward, downtitrate O2 as
tolerated as the patient is stabilized.As a
167
general rule, patients meeting criteria for any
of the following parameters may be classified
as having acute respiratory failure:
pH < 7.25
PaO2 < 50
PaCO2 > 50
PaO2/FiO2 ratio < 250
Other criteria may include the following:
Altered mental status
Tidal volume < 250 ml
Clinical Pearls
Some clinicians affectionately refer to
meeting these criteria as being in the “50/50
club.”
Capnography
Capnography helps evaluate the adequacy of
ventilation and blood flow by measuring
end-tidal CO2 (PetCO2). PetCO2 is the
maximum concentration of CO2 at the end of an
exhaled breath. Two common methods of
measurement are by using colorimetric devices
168
or by measuring actual CO2 molecules. CO2
molecule
measurement
(called
infrared
absorption spectrophotometry) provides a
waveform (called a capnogram) and is the more
useful application for ongoing monitoring in the
ICU. This method of ongoing monitoring is
reviewed in the following sections.
Monitoring ventilation with PetCO2
Monitoring PetCO2 levels is considered to be a
more objective method of assessing ventilation
than respiratory rate or the subjective
evaluation of respiratory depth (American
Academy of Pediatrics, Committee on Drugs,
2002; American Society of Anesthesiologists
Task Force on Sedation and Analgesia by
non-Anesthesiologists, 2002; Cacho et al.,
2010; Greensmith and Aker, 1998; Lightdale et
al., 2006; Soto et al., 2004; Vargo et al., 2002).
The normal range for PetCO2 can be considered
as 35–45 mmHg. Ideally, however, a patient’s
true PetCO2 baseline should be validated by the
PaCO2 on the ABG. PetCO2 and PaCO2 values
should trend similarly. Deadspace ventilation
accounts for an expected 5 mmHg gradient
between the two, with the PetCO2 being lower,
provided the patient has healthy lungs. Patients
with lung disease such as COPD often have
wider PetCO2–PaCO2 gradients. Regardless,
PetCO2 levels greater than 50 mmHg or
increases of ≥10 mmHg above baseline require
pH evaluation via ABG as well as interventions
169
to support the airway and breathing until the
patient is considered safe. Applications include
monitoring of patients during ventilator
weaning, detecting incorrect placement of
endotracheal
tubes,
and
detecting
disconnection from the ventilator. Studies
regarding additional uses, such as detecting
correct placement of nasogastric tubes, are
ongoing.
Figure 3.5 illustrates phases of the capnogram,
the PetCO2 waveform displayed on the patient
monitor. Monitors also display a respiratory
rate (e.g., the number of capnograms per
minute). Waveform characteristics reveal
information regarding ventilation, for example,
hypopnea (small waveform), apnea (no
waveform), or obstructive disease such as
asthma (“shark-fin” type pattern).
Figure 3.5 Phases of the capnogram.
170
Monitoring blood flow
A normal PetCO2 reading depends upon
adequate blood flow to the lungs. Therefore, a
decrease (particularly a sudden decrease) in
PetCO2 without an associated increase in
minute ventilation may suggest a decrease in
cardiac output, such as bleeding, heart failure,
or increased deadspace (e.g., pulmonary
embolus). In these situations, measurement of
cardiac output and stroke volume or ABG
testing and chest imaging should be considered
in order to validate findings.
PetCO2 values have also shown to be prognostic
indicators in cardiac arrest. PetCO2 levels less
than
10
mmHg
after
20
min
of
cardiopulmonary resuscitation (CPR) have been
associated with 0% survival (Ahrens et al.,
2001; Levine, Wayne, and Miller, 1997). In
addition, increased PetCO2 levels obtained
during CPR have been associated with adequacy
of chest compressions and return of
spontaneous circulation.
Modes of mechanical ventilation
Management
protocols
for
mechanical
ventilation have been studied for decades.
Critical care teams generally select modes of
mechanical ventilation that optimally manage a
patient’s unique physiologic requirements.
Surveillance of patient trends and values
171
requires
strong
multidisciplinary
work,
including airway management, sedation
protocols, activity coordination, and nutritional
support. The modes of mechanical ventilation
and airway support systems with monitoring
strategies are reviewed later. There is strong
support for multidisciplinary management
using weaning protocols for liberating patients
from mechanical ventilation (Brook et al., 1999;
Ely et al., 2001; MacIntyre, 2008; MacIntyre et
al., 2001). However, ascertaining readiness for
weaning is highly individualized and complex,
especially if patients have multiple comorbid
conditions or prolonged debilitation.
Continuous positive airway pressure
(CPAP) with pressure support
This mode is commonly used during the last
phase of weaning trials. No mandatory
ventilator breaths are delivered, only
patient-triggered spontaneous tidal volumes
with the aid of PEEP and pressure support are
given to support the patient’s spontaneous
breathing cycles. This mode facilitates
spontaneous breathing and overcomes airway
resistance of the endotracheal tube and the
ventilator
circuit.
This
is
generally
accomplished with a pressure support between
5 and 10 cm H2O.
172
Synchronized intermittent mandatory
ventilation (SIMV)
Machine-delivered tidal volumes are delivered
at a set volume and minimum mandatory rate
entered by the clinician. Breaths can be patientor ventilator-triggered. However, in between
mandatory tidal volume ventilator breaths, the
patient can pull spontaneous tidal volumes as
well with the assistance of PEEP and pressure
support.
Assist/control ventilation (AC)
Machine-delivered tidal volumes are delivered
at a set volume and minimum mandatory rate
set by the clinician. These breaths can be
patient- or ventilator-triggered. The main
difference between AC and SIMV is that in AC,
ALL ventilator breaths are delivered at the
mandatory, preset tidal volume. Therefore, the
work of breathing in AC is less as opposed to
SIMV. Graphics illustrating the differences
between CPAP with pressure support, SIMV,
and AC are displayed in Figure 3.6.
173
Figure 3.6 CPAP, PS, and AC patterns.
Pressure control ventilation
A minimum mandatory rate is set by the
clinician;
however,
tidal
volumes
are
patient-specific. Rather than tidal volumes
predetermined by set volume, they are
determined according to mean airway pressure.
The ventilator will deliver the tidal volume until
a preset pressure is achieved and then stop the
inspiratory flow. Advantages of pressure control
include the minimization of volutrauma and
barotrauma associated with AC ventilation.
Airway pressure release ventilation
(APRV)
This mode is characterized by higher baseline
airway pressures, which may be viewed as a
nearly
continuous
alveolar
recruitment
174
maneuver. Airway pressure then periodically
drops to zero, aiding in carbon dioxide
elimination and theoretically stimulating the
diaphragm in order to eventually facilitate the
weaning process. This mode allows unrestricted
spontaneous
breathing
throughout
the
respiratory cycle.
Pressure-regulated volume control
(PRVC)
This mode is an AC/pressure control hybrid.
Volumes will be delivered at a preset amount as
in AC, to a preset pressure limit as in pressure
control, or whichever occurs first during a
particular breath.
Inverse ratio ventilation
The normal physiologic inhalation time/
exhalation time (I/E) ratio is 1:3. The use of
inverse ratio ventilation involves increased
inspiratory times delivered by the ventilator
and expiratory times are decreased to achieve
I/E ratios of less than 1:3 to as much as 1:1. This
mode is part of a strategy to improve PaO2 and
SaO2 levels by prolonging the inhalation phase.
Patients must be paralyzed and sedated to
tolerate this process due to comfort concerns
created
by
such
an
unnatural
inhalation–exhalation pattern. Caution must be
taken to avoid hyperinflation.
175
Oscillatory ventilation
This mode is associated with respiratory rates
of 150–300 breaths per minute (i.e., Hertz, or
“cycles” per minute) and tidal volumes of
approximately 50 ml (determined by the
“amplitude” setting). A set airway pressure is
determined by the clinician. This mode is often
used in severe ARDS in order to avoid the risk
of volutrauma and barotrauma that may be
associated with AC or pressure control modes.
Patients ventilated according to this mode
should be paralyzed and sedated via continuous
infusion.
Overview of protective lung ventilation
in ARDS
The ARDS Network is a collaborative designed
to
facilitate
knowledge
transfer
and
protocolization regarding evidence-based care
for patients with ARDS. The National Heart,
Lung, and Blood Institute as well as the
National Institutes of Health collaborate within
the ARDS Network to determine best practice
for ARDS management (NHLBI ARDS
Network, 2014).
Inclusion criteria include the acute onset of
ARDS
PaO2/FiO2 ≤ 300
Bilateral (patchy, diffuse, or homogeneous)
infiltrates consistent with pulmonary edema
176
No clinical evidence of left atrial
hypertension
Guidelines for ventilator setup and adjustment
Calculate predicted body weight (PBW):
Select AC mode.
Set initial TV to 8 ml/kg PBW.
Reduce TV by 1 ml/kg at intervals ≤ 2 h until
TV = 6 ml/kg PBW.
Set initial rate to approximate baseline
minute ventilation (not > 35 bpm).
Adjust TV and RR to achieve pH and plateau
pressure goals given later.
Set inspiratory flow rate above patient
demand (usually > 80 l/min).
ARDSNet protocol goals
Oxygenation goal: PaO2 55–80 mmHg or
SpO2 88–95% (NHLBI ARDS Network,
2008)
Use incremental FiO2/PEEP
combinations to achieve goal. Higher
PEEP levels will decrease FiO2 and may
be preferred in patients with high FiO2
who can tolerate higher PEEP (stable BP,
no barotrauma).
177
Plateau pressure goal: ≤30 cm H2O
Low tidal volume strategy to avoid
volutrauma and barotrauma
pH goal: 7.30–7.45
“Permissive hypercapnia”—a strategy
designed to avoid overventilating the
patient and that allows the pH to be
maintained modestly at less than 7.35 to
avoid barotrauma.
“clinical pearl”—patients will generally
tolerate permissive hypercapnia (pH ~
7.2, oxygen saturation < 90% to
85–90%).
I/E ratio goal: 1:1.0–1:3.0
Monitoring for complications
during mechanical ventilation
High peak airway pressures on
mechanical ventilation
High peak airway pressures (>30–40 cm H2O)
require immediate attention as potential causes
may range from minor to life-threatening.
Causes essentially range from least severe to
most severe and may include the following:
Coughing. Consider suctioning, sedating, or
administering a bronchodilator.
Bronchospasm: Bronchodilator may be needed.
178
Patient–ventilator asynchrony: Patient may
need sedation or ventilator settings to be
adjusted.
Excessive set tidal volumes being administered.
Right mainstem intubation (right mainstem
bronchus is at a more obtuse angle than the
left).
Mucous plugging.
Pneumothorax.
Endotracheal tube occlusion.
High peak airway pressures may be resolved
with medication (e.g., sedation, analgesia),
suctioning, or adjusting ventilator settings.
However, airway pressure alarms associated
with acute changes in tidal volume, minute
ventilation, vital signs, or decreased SaO2
should
immediately
be
evaluated
by
disconnecting the patient from the ventilator
and ambu bagging with 100% O2.
Response to bagging—monitoring and
treatment
If bagging the patient is NOT difficult, the
patient can be placed back on the ventilator.
The patient should be reevaluated for the need
for sedation, a change in ventilator settings, or
bronchospasm, and treated accordingly.
If bagging the patient IS difficult, the airway
must be evaluated for obstruction or another
179
cause
of
diminished
air
movement.
Determination of the underlying cause can be
facilitated by the advancement of a coudé
suction catheter through the endotracheal tube.
If the suction catheter CANNOT be passed
through the endotracheal tube, assess for
biting. Increasing the sedation and bite blocks
may enable resolution of these obstructions.
Thick mucous plugs or clots blocking the airway
may be loosened with aggressive bagging and
lavaging with saline. Emergent bronchoscopy
may be considered; however, patients who
continue to deteriorate may need to be
extubated so that a new endotracheal tube can
be placed. If the suction catheter CAN be
passed,
consider
bronchospasm,
pneumothorax, right mainstem intubation, or
obstruction in the tracheobronchial tree lower
than the endotracheal tube itself.
Auto-PEEP effect
Mechanically ventilated patients require
adequate expiratory time to avoid barotrauma
and hyperinflation injury. Inadequate airflows,
excessive tidal volumes, narrow endotracheal
tubes, water clogging ventilator circuits, and
high respiratory rates limit expiratory time and
place the patient at risk for an “air-trapping”
condition termed auto-PEEP (see Fig. 3.7).
Auto-PEEP can be determined by performing
an expiratory hold maneuver on the ventilator.
Risks of auto-PEEP include reduction of venous
180
return, hypotension, increased work of
breathing, and patient–ventilator triggering
difficulty.
Figure 3.7 Auto-PEEP effect.
Auto-PEEP can be corrected by adding extrinsic
(set) PEEP, lowering tidal volumes, sedating in
some cases, and prolonging exhalation times
(or decreasing inhalation time) of the ventilator
I/E ratio.
Weaning from mechanical
ventilation
The majority (~70%) of patients on ventilators
can be weaned successfully in a single weaning
period (Luetz et al., 2012). MacIntyre and
colleagues (2001) published an evidence-based
review and guidelines for ventilator weaning,
including criteria to be utilized during
181
spontaneous breathing trials and weaning
protocols. Evidence-based guidelines have also
been published specifically for nonphysician
providers (Ely et al., 2001). Table 3.2 is based
on those criteria. Several randomized trials
have shown that weaning protocols driven by
registered nurses (RNs) and respiratory
therapists (RTs) improved efficiency of weaning
as opposed to physician-directed weaning
(Blackwood et al., 2010; Ely et al., 2001).
Although these guidelines may appear
seemingly dated, they have been described as
having stood the “test of time” (MacIntyre,
2008) and updates have not been published.
However, to date no data have shown which
specific weaning strategy is best (e.g., CPAP and
pressure support ventilation (PSV) versus
T-piece), much like no specific weaning
protocol has been shown to be better than
another.
Table 3.2 Parameters for liberating (weaning)
from mechanical ventilation.
Weaning
parameter
Reference range
Respiratory rate <30 breaths/min
Spontaneous
tidal volume
325–400 ml (4–6 ml / kg)
Minute
ventilation (VE)
<10–15 l/min
182
Weaning
parameter
Reference range
Negative
−20 to −30 cm H2O
inspiratory force
(NIF)
pH
≥7.25
SaO2
≥90%
PaO2
≥60 mmHg
FiO2
Requiring <0.40–0.50
PaO2 / FiO2
ratio
>150–200
PEEP
Requiring <5–8 cm H2O
Rapid shallow
breathing index
(respiratory
rate/tidal
volume)
<100 breaths/min/l
Hemodynamic
stability
As evidenced by minimal or
low-dose vasopressor
therapy and absence of
active myocardial ischemia
Secretions
Minimal secretions,
adequate cough effort
Heart rate
≤140
Blood pressure
Stable with no (or minimal)
vasopressors
183
Weaning
parameter
Reference range
Mental status
For example, arousable,
Glasgow Coma Scale (GCS)
≥ 13, and/or no continuous
sedative infusions
Evidence of some reversal of the underlying
cause of the respiratory failure
Regardless of the specific weaning strategy
used, the ultimate goal is to wean to extubation
as soon as the patient can safely tolerate it. This
is because mechanical ventilation itself is not
without risk. Complications are common,
including ventilator-associated pneumonia,
deep vein thrombosis, paralytic ileus,
deconditioning, skin breakdown, and vocal cord
paralysis. A daily weaning readiness evaluation
should be performed for possible spontaneous
breathing trial based on criteria such as those
listed in Table 3.2, provided the underlying
cause of respiratory failure is improved or
resolved.
Research also clarifies that daily interruption of
continuously infusing sedatives leads to
decreased ventilator days when compared to
controls, and that intermittently given sedation
leads to shorter vent days compared with
continuous infusion of sedation (Brook et al.,
1999; Grap et al., 2012; Kress et al., 2000;
184
Luetz et al., 2012; Roberts, Haroon, and Hall,
2012).
Some patients will exhibit respiratory failure
shortly after extubation despite excellent
objective evaluation of readiness and
appropriate precautions. These patients may be
more appropriate for tracheostomy. Although
an optimal rate of reintubation is not known,
5–15% has been published as a “healthy” 24-h
failure rate (e.g., reintubation rate) for
non-neurologically impaired ICU patients (Ely
et al, 2001). Higher than 15% may be reflective
of weaning that is perhaps too aggressive and
less than 5% may not be aggressive enough.
Clinical pearls
For difficult-to-wean patients (48–72 h after
resolution of the underlying cause of
respiratory failure), consider applying the
WEANS NOW checklist or the Burns Wean
Assessment Program (BWAP) protocol to
help ensure that all barriers to wean ability
are being addressed (Burns et al., 2010). In
prior testing, a score of 50 on the BWAP was
predictive of successful weaning. Burns et al.
(2010) retrospectively analyzed over 1800
patients on whom the BWAP had been
prospectively applied and found that 88% of
weaning attempts were successful (Burns et
185
al., 2010). The BWAP is designed to assess 12
items as general assessment indicators,
including metabolic factors, sleep, and
general body endurance, and 14 items that
assess respiratory assessment parameters
(Burns et al., 2010). For the WEANS NOW
checklist, see Table 3.3.
Table 3.3 WEANS NOW checklist to assess
failure to wean 48–72 h after resolution of
underlying condition causing respiratory
failure.
Modified from Green et al. (2004).
Weaning
parameters
Readiness to wean (see
Table 3.2)
Endotracheal
tube
Ideal to use largest ET tube
possible
Consider use of PSV+
during SBT to overcome
intrinsic resistance of ET
tube
186
Weaning
parameters
Readiness to wean (see
Table 3.2)
Aterial blood
gases
Prevent or treat metabolic
alkalosis
Maintain PaO2 at 60–65
mmHg to avoid blunting of
respiratory drive
For CO2-retaining patients,
keep PaCO2 at or above
their baseline
Nutrition
Provide nutritional support
as needed
Avoid electrolyte
imbalances
Avoid excessive caloric
intake (may increase CO2
production)
Secretions
Clear regularly
Avoid dehydration if
possible
187
Weaning
parameters
Readiness to wean (see
Table 3.2)
Neuromuscular Avoid agents that may
factors
exacerbate neuromuscular
weakness in at-risk patients
(neuromuscular blockers,
aminoglycosides,
clindamycin)
Avoid unnecessary
corticosteroids
Obstruction of Bronchodilator use as
airways
appropriate
Rule out possibility of
foreign bodies in airway
Wakefulness
Avoid oversedation
Wean in morning or when
patient is most awake
ET, endotracheal; PSV, pressure support
ventilation; SBT, spontaneous breathing trial.
Clinical pearls
Ventilator weaning for acute-on-chronic
respiratory failure (e.g., COPD exacerbation)
188
may be facilitated by the use of noninvasive
positive pressure ventilation (NIPPV).
Postextubation stridor: monitoring and
treatment
Postextubation stridor is an emergent condition
and is documented to occur in up to 16% of
patients (usually occurring in <15 min after
extubation) (Critical Care Alert, 2012). This
obstruction is usually related to laryngeal
edema and treatment is aimed at initiating local
vasoconstriction and reducing airway edema.
First-line
treatment
includes
airway
precautions
and
nebulized
(racemic)
epinephrine. The literature also suggests that
humidified O2, the cuff leak test, parenteral
steroids, laryngeal ultrasound, and inhalation
of an oxygen/helium mixture may help avoid or
alleviate postextubation stridor, although
randomized controlled trials would be needed
to definitively confirm the efficacy of these
treatments (Cheng et al., 2011; Ding, Wang, and
Wu, 2006; Jaber et al., 2009; Markovitz,
Randolph, and Khemani, 2009; Wittekamp et
al., 2009).
Patients with vocal
longer-term intubation
“looser,” upper airway
not appear in as much
cord paralysis after
display a lower pitched,
sound and typically do
distress, although these
189
sounds may sometimes be confused with
stridor. However, these patients must be
evaluated for swallowing dysfunction to gauge
the risk of aspiration.
Noninvasive positive pressure
ventilation
NIPPV may be used in select patients as a
strategy to avoid placement of an advanced
airway (but should not be used to delay
imminent intubation). NIPPV provides close to
full mechanical ventilatory support with the
settings of a conventional ventilator (can be
pressure-cycled or volume-cycled modes) used
via a tight-fitting mask (can be a mouth or nasal
mask). A mouth mask may be preferred over a
nasal mask due to the increased airway
resistance of the nasal passages and the
likelihood of positive pressure loss through the
mouth, which may also be perceived as
uncomfortable for the patient. Monitoring and
adjusting the mask to attain a good seal and fit
is key in order to maintain comfort and
minimize air leak, positive pressure loss, eye
drying, and skin breakdown.
Hypercapnic respiratory failure tends to
respond well to NIPPV. The literature has
shown improved outcomes with regard to
COPD exacerbations, cardiogenic pulmonary
edema, and hypoxemic respiratory failure in
immunocompromised hosts with pulmonary
190
infiltrates (Esteban et al., 2008; Keenan et al.,
2011; Kollef et al., 2008). However, in general,
hypoxemic respiratory failure doesn’t respond
as well to NIPPV. The American Association of
Respiratory Care has criteria for which to
consider NIPPV in patients with COPD
exacerbation (see Table 3.4).
Table 3.4 American Association of Respiratory
Care criteria for noninvasive positive pressure
ventilation for exacerbation of COPD.
Must meet two or more of the following
and have no contraindications
Respiratory distress with
moderate-to-severe dyspnea
Arterial pH < 7.35 with PaCO2 > 45
Respiratory rate ≥ 25 breaths/min
Contraindications to NIPPV primarily include
instability or inability to maintain an airway
such as the following:
Cardiac or respiratory arrest, or unstable
cardiac rhythm
Hemodyamic instability
Nonrespiratory organ failure
Facial surgery, trauma, or deformity
Severe encephalopathy or inability to protect
airway
191
Upper airway obstruction
Severe upper GI bleeding, risk for aspiration, or
inability to clear secretions
Patients who fail NIPPV require endotracheal
intubation and mechanical ventilation, pending
the patient’s code status. Signs of failure of
NIPPV therapy include the following:
Worsening gas exchange (should see
improvement on ABG within 1 h)
Worsening tachypnea, dyspnea, or asynchrony
with mechanical breaths
Hemodynamic instability
Mental status changes
Even if the patient responds to NIPPV therapy,
close ongoing monitoring is critical in order to
evaluate for potential decline in status.
Clinicians must continue to watch for changes
in mental status, respiratory rate, accessory
muscle use, tidal volumes, ventilator synchrony,
and comfort. When in doubt of potential
deterioration, obtain an ABG and do not be
misled by a seemingly normal SaO2, because
desaturation is often a late sign of patient
changes.
Tension pneumothorax
Tension pneumothorax is a cause of obstructive
shock and is a medical emergency. In the
intensive care setting, pnueumothorax more
192
commonly occurs as a complication of
mechanical ventilation, central line placement,
or status post thoracentesis. A tension
pneumothorax in patients with these problems
results when air enters the pleural space via a
tear in the lung or tracheobronchial tree and is
not allowed to escape during expiration,
creating a one-way valve effect. Intrathoracic
pressure then builds which compresses the
heart and great vessels and decreases venous
return. Signs and symptoms include tachypnea,
dyspnea, hypoxia, tachycardia, hypotension,
restlessness, agitation, absent breath sounds
and hyperresonance on the affected side and
tracheal deviation toward the contralateral side.
Emergent treatment—needle thoracostomy
Urgent decompression must be done by
inserting a large bore needle (16 gauge is good,
14 gauge is better) in the second intercostal
space, midclavicular line. Conventional chest
tube placement should immediately follow.
Clinical Pearls
Cutting off the finger and fingertip of a
rubber glove and securing it over the end of
the angiocath will create a rudimentary
one-way valve until the chest tube can be
placed (glove will collapse over the end of the
193
angiocath during inspiration). A three-way
stopcock can also serve as a valve, but will
have to be turned periodically to allow air to
escape.
Chest radiograph interpretation
The chest radiograph may be the most
frequently performed imaging study in the
critical care unit. A significant amount of
information may be obtained from the
radiograph; however, a systematic approach to
interpretation is recommended in order to
avoid clinical concerns going unrecognized.
Radiologic criteria for evaluation may be
broken down into five areas:
Heart size and configuration—a
cardiothoracic ratio of 0.60 is the upper
limit of normal, greater than 0.60 may
suggest cardiomegaly.
Pulmonary vascularity—normal lung fields
have a light, white, “lacey” appearance.
Heavier interstitial lung markings or
generalized haziness over the lung fields
may suggest pulmonary edema.
Aeration of the lungs—overall exapansion,
radiolucency, and density of the right and
left lungs should be equal.
194
Lung infiltrates—observe for the presence or
absence of pulmonary infiltrates (areas of
increased densities). Types of densities and
their distribution may lead to a diagnosis.
Mediastinal shift—the trachea, heart, and
great vessels shift toward the side with the
decreased lung volume or away from the
hemithorax with increased lung volume.
It is important to remember that even though
the lungs may be the primary focus for
obtaining the film, all areas of the radiograph
warrant evaluation including the air-filled
spaces, soft tissue, and all bony structures.
Other aspects to evaluate include (i) liver size
(may vary with the progression of right-sided
heart failure), (ii) abdominal gas pattern, (iii)
catheter tube and position, (iv) bony structure
(evaluate
for
fractures,
dislocation,
hypodensities, and bony anomolies), and (v) it
is also important to know the age of the patient
and progression of any previous radiologic
findings. Figure 3.8 shows an illustration of
normal landmarks.
195
Figure 3.8 Common landmarks and structures
of the chest radiograph. (a) Projection and the
lateral. (b) Projection.
From Ferri (2004). © Elsevier.
Pathologies commonly encountered in the ICU
that may be identified on the chest radiograph
include the following:
ARDS—Generalized, bilateral pulmonary
infiltrates (“ground glass” appearance,
progressing to complete white-out) known as
196
noncardiogenic pulmonary edema. In order to
differentiate from heart failure, normal brain
natriuretic peptide (BNP) and/or pulmonary
artery wedge pressure less than 18 mmHg help
confirm ARDS.
Pleural effusion—Characteristics include
blunting of costophrenic angle in an upright
patient, suggesting fluid accumulation.
Pneumothorax—A portion of the lung border
appears to be shifting toward the mediastinum,
leaving a fully dark, delineated area between
the lung border and preexisting lung field.
Pneumothorax can occur anywhere along the
lung border, but is most common in the apices.
“White out” areas—May be due to blood
(hemothorax), severe atelectasis, or mucous
plugging.
Describing infiltrates—Infiltrates should be
described according to their distribution. For
example, symmetrical versus asymmetrical,
diffuse versus nondiffuse, alveolar (ill-defined
margins), or interstitial (stringy appearance).
Clinical Pearls
Be aware that the pulmonary vasculature
may be obscured on supine chest x-rays,
because blood is no longer flowing
dependently to the lower lobes.
197
Sleep-disordered breathing in the
critical care unit
Normal sleep can affect respiratory physiology
in several ways, including decreased hypoxic
ventilatory drive, decreased hypercapnic
ventilatory drive, increased airway resistance,
and increased arousal threshold to increased
airway resistance. The addition of comorbidities
(e.g., COPD) can exacerbate this otherwise
normal physiology. Sleep issues abound in
critical care units (Hardin, 2009). Sleep
disorders that impact patients in the ICU
include obstructive sleep apnea (OSA), central
sleep apnea (CSA), and obesity hypoventilation
syndrome (OHS). However, sometimes the
primary pathology occurs as repeated upper
airway collapse during sleep (Dhand, 2010).
The obesity epidemic and increased recognition
of how sleep disorders exacerbate/cause heart
disease have contributed to the growing field of
sleep
medicine,
and
should
increase
practitioners’ surveillance of and monitoring for
these disorders (Dhand, 2010). While few
monitoring guidelines have been published,
perioperative management of patients with
obstructive sleep apnea–hypopnea syndrome
(OSAHS) has been advanced by the American
Society of Anesthesiologists Task Force on
Perioperative Management of Patients with
Obstructive Sleep Apnea (2006). These include
avoidance of systemic opiods when possible,
198
supportive use of postextubation oxygenation,
CPAP and NIPPV application as soon as
feasible after surgery, avoidance of supine
positioning of patients with OSA, and
continuous pulse oximetry until room air SaO2
remains greater than 90% during sleep.
Obstructive sleep apnea
OSA is characterized by excess soft tissue in the
upper airway that limits airflow and results in
obstruction, which has been associated with
postoperative complications, increased ICU
admissions, onset of inpatient delirium, and
greater length of hospital stay (Chung et al.,
2008). Hypopneas (resulting in reductions of
tidal volume by 50% with breaths and generally
accompanied by at least a 4% decline in oxygen
saturation) and apneas (no tidal volume) cause
repeated disruptions in progression through the
sleep cycle and microarousals (Bradley and
Floras, 2009). Sleep disruptions in the ICU
setting are significant, particularly in
mechanically ventilated patients and have been
studied extensively over the past several
decades (Cabello et al., 2008; Freedman et al.,
2001; Frighetto et al., 2004). Sleep quality is
also significantly affected by sedatives in ICU
patients (Frighetto et al., 2004). Although
difficult to use in the ICU, polysomnography
studies have shown significant disruptions of
sleep architecture in ICU patients (Cabello et
al., 2008; Parthasarathy and Tobin, 2002) and
199
nurse observations and actigraphy have not
been validated as alternatives in the ICU
(Beecroft et al., 2008). Sleep disturbances have
been linked to higher rates of stress hormones,
inflammatory
mediators,
and
cardiac
arrhythmias (Bijwadia et al., 2009; Ryan et al.,
2008).
Alonso-Fernandez et al. (2005) also found an
increased frequency of ST-segment depression
indicative of myocardial ischemia in patients
with OSAHS compared with controls. In
addition,
OSAHS
patients
had
more
arrhythmias and elevated daytime urinary
epinephrine levels. Redeker (2008) reviewed
the many challenges to research sleep
measurement in the critical care setting,
including physiologic monitoring and scoring of
sleep variables, impact of multiorgan
dysfunction and interventional treatments, and
challenges in accurate detection of behavioral,
perceptual, and temporal variations in sleep
patterns.
Obstructions during the sleep cycle result in
paradoxical respiratory effort and apneas that
lead to increased arousals and desaturations.
OSA can be classified by severity according to
the apnea–hypopnea index. Patients exhibit
daytime sleepiness because of increased stress
hormones and nighttime catecholamine surges.
Long-term effects have been linked to
200
hypertension, heart failure, and stroke (Epstein
et al., 2009).
OSA impacts the course of hospitalization in the
ICU because it is a risk factor for respiratory
failure and is largely undiagnosed. It is
estimated that nearly 80% of men and 93% of
women with moderate to severe OSA are
undiagnosed
(Chung
et
al.,
2008).
Endotracehal intubation of these patients is
challenging due to a crowded oropharynx and
may require the assistance of a video scope or
bronchoscopy.
Central sleep apnea
CSA is more commonly associated with heart
failure. It differs from OSAHS in mechanism
and presentation, is generally diagnosed by
polysomnography, and is associated with apnea
in the absence of rib cage or abdominal
movements. Grimm et al. (2009) found that
CSA is common in patients with implantable
cardioverter defibrillators (ICDs), detected in
57 of 129 (44%) patients with first ICD implant.
While OSAHS was also diagnosed in 25% of
patients, CSA patients were found to have more
severe cardiomyopathy (57% versus 26% of
patients with OSA). Serizawa et al. (2008) also
studied 71 patients with polysomnography
within 1 week after ICD and found
sleep-disordered breathing diagnosis in 47 of 71
(66%). Sleep-disordered breathing predicted
201
life-threatening arrhythmias that occurred most
often during sleep.
Ryan and colleagues (2008) found that the
timing of ventricular ectopy differed during
sleep-disordered breathing, with the majority of
ventricular arrhythmias occurring during the
apneic/hypopneic phases in patients with
OSAHS and during hyperventilatory stages in
patients with CSA. Although a number of
mechanisms may account for these alterations,
the definitive cause remains unknown.
Obesity hypoventilation syndrome
OHS is a consequence of morbid obesity. The
hallmark sign of OHS is “awake hypercapnia
(PaCO2 > 45 mmHg) in the obese patient (BMI
> 30 kg/m2) after other causes that could
account for awake hypoventilation, such as lung
or neuromuscular disease, have been excluded”
(Piper and Grunstein, 2011, p. 292). Nowbar et
al. (2004) identified the prevalence of OHS in
approximately 50% of patients weighing over
50 kg/m2 and the growing proportion of obesity
in the United States predicts rising frequency of
this disorder. The majority of patients with this
condition have complex interactions of altered
central respiratory drive, upper airway
obstruction and resultant increased work of
breathing, and hormonal influences (Piper and
Grunstein, 2011). Treatment with CPAP and
reductions in CO2 are generally effective.
202
Expiratory positive airway pressure (EPAP)
may be added if continued problems with
oxygen saturation or hypercapnia are not
resolved with CPAP. Long-term management
with tracheostomy or bariatric surgery may also
be indicated although further outcome studies
are needed.
While OHS is characterized by daytime
hypercapnia, actual definitions vary in the
literature. Signs and symptoms of OSA and
OHS can be systematically identified with
screening strategies such as the “STOP-BANG”
questionnaire (Abrishami, Khajehdehi, and
Chung, 2010; Chung et al., 2008).
Questionnaires can be valuable tools for quick
prediction of sleep disorders as they can be
applied and scored easily as part of routine
daily practice. The “STOP-BANG” is considered
to be a questionnaire with strong positive
predictive value based on the high-quality
methodology of its validation studies
(Abrishami, Khajehdehi, and Chung, 2010;
Chung et al., 2008). Questions from this tool
include the following:
Do you snore loudly? (louder than talking or
loud enough to be heard through closed
doors?
How loud do you snore? (can it be heard in
another room?) How often do you snore?
Has your snoring ever bothered anyone?
203
Do you often feel tired, fatigued, or sleepy
during the daytime?
How often do you feel tired or fatigued after
you sleep?
During your waking time, do you feel tired,
fatigued, or not up to par?
Has anyone noticed that you quit breathing
during your sleep?
Do you have or are you being treated for
high blood pressure?
Have you ever nodded off or fallen asleep
while driving a vehicle? If so, how often?
(Chung et al., 2008, p. 816)
Heightened
awareness
of
the
clinical
manifestations of sleep-disordered breathing in
critically ill adults is necessary for accurate
monitoring and anticipation of risk.
The
STOP-BANG
questionnaire
is
a
standardized patient screening using yes/no
questions that risk-stratifies patients for OSA
based on the number of “yes” responses
observed. Answering “yes” to less than three
questions indicates that a low risk of OSA
exists. Obtaining positive answers to three or
more questions indicates a high risk of OSA.
Questionnaires such as this can be
implemented using protocols for appropriate
patient placement (floor versus step-down
versus ICU) to prevent adverse outcomes
204
(Dhand, 2010). Patients with a pH < 7.30,
altered mentation, or intolerant of positive
pressure ventilation should be admitted to the
ICU (Lee and Mokhlesi, 2008). Medication
management of these patients should include
limiting the administration of sedating
medication that may exacerbate potential
airway compromise. Patients at high risk
should also be considered for further
assessment by a sleep specialist, use of airway
precautions, and CPAP or BiPAP therapy as
appropriate while in the ICU and while
screened for perioperative risk factors. In fact,
more recent data suggest that long-term
positive pressure ventilation for OHS is
associated with mortality benefit (Priou et al.,
2010).
CPAP and BiPAP therapy
A first-line approach for treating obstructive
sleep disorders in the ICU is often CPAP or
BiPAP therapy. CPAP is essentially a positive
pressure delivery system that applies PEEP via
a tight-fitting facemask or nasal appliance (i.e.,
“nasal pillows”) in order to maintain an open
airway during sleep. PEEP delivered in this
setting may also be referred to as EPAP. CPAP
is generally not considered a therapy designed
to correct hypercapnia, unless the hypercapnia
is due solely to uncomplicated OSA.
BiPAP provides an increased amount of
ventilatory support over CPAP and is the
205
preferred method between the two to treat
more complex hypercapnia. The increased
ventilatory support in BiPAP is due to the
combination of inspiratory positive airway
pressure (IPAP) and EPAP it provides. IPAP
lessens work of breathing by delivering flow
during inspiration to a predetermined airway
pressure. The IPAP minus the EPAP (i.e., the
“delta”) correlates with tidal volumes and the
degree of ventilation (Lee and Mokhlesi, 2008).
BiPAP modes may consist of time-cycled,
machine-triggered breaths, spontaneous, or a
combination.
Without data from a sleep study to diagnose the
sleep disorder and titrate CPAP or BiPAP
settings, little evidence exists to guide initial
settings to start BiPAP and CPAP therapy.
Typical initial settings may be an EPAP of 5–7
cm H2O for CPAP and an IPAP/EPAP of 10–12
cm H2O over 5 cm H2O for BiPAP. CPAP and
BiPAP initiated empirically should be followed
with continuous cardiac and pulse oximetry
monitoring, and ABGs as optimal settings are
being determined. Failure to titrate pressure
settings high enough to overcome airway
obstruction
could
result
in
apneas,
desaturations, or even death. One can
reasonably assume that patients with severe
OSA or OHS will require higher pressures.
However, pressures titrated too high may result
in patient discomfort, gastric distension, mask
leak, eye dryness, and skin irritation. More
206
specific pressure titration guidelines can be
found on the American Academy of Sleep
Medicine web site (Morgenthaler et al., 2008).
Patients already diagnosed with OSA or OHS
prior to admission should be instructed to have
their home CPAP device brought to the hospital
(to use while sleeping during the day as well as
at night). One may consider tracheostomy in
OSA patients refractory to CPAP and BiPAP but
this is generally a last resort (Dhand, 2010).
Airflow through a tracheostomy allows the
patient to completely bypass the upper airway
soft tissue that causes the obstruction. Table 3.5
displays a general guide to empirically initiating
CPAP or BiPAP according to the sleep disorder.
Table
3.5
Treatment
options
for
sleep-disordered breathing in the critical care
unit (assuming data from prior sleep study is
not available).
Sleep
disorder
Treatment
OSAHS
without
associated
hypercapnia
CPAP with close monitoring
that includes continuous
pulse oximetry and telemetry
Hypercapnia
related to
OSAHS alone
CPAP at a pressure that
resolves obstructive events to
correct hypercapnia (with
continuous monitoring as
above)
207
Sleep
disorder
Treatment
Hypercapnia
BiPap generally required
that involves
(with continuous monitoring
sleep-related
as above)
hypoventilation
BiPAP, CPAP plus end-expiratory airway
pressure; CPAP, continuous positive airway
pressure;
OSAHS,
obstructive
sleep
apnea–hypopnea syndrome.
Cardiovascular aspects to monitor include an
increase in myocardial oxygen demand during
sleep-disordered breathing. Systemic blood
pressure can surge up to as high as 250/150
mmHg during post-apnea arousal (Naughton,
2008). This state of elevated afterload is
implicated in OSA-associated chronic heart
failure.
Approach to cardiogenic dyspnea in
acute heart failure
The advent of the serum BNP measurement has
significantly aided clinicians to differentiate
cardiogenic versus noncardiogenic forms of
pulmonary edema (Hunt et al., 2009). BNP is
released in response to increased preload and
stretch of ventricular tissue. BNP levels less
than 250 mg/ml may indicate acute lung injury
and help rule out heart failure as a cause of
dyspnea. Serum levels of BNP > 250 mg/ml are
208
suggestive of decompensated heart failure,
reduced ejection fraction (Hunt et al., 2009),
and may serve as a prognostic indicator in heart
failure risk stratification. Although laboratory
references may suggest that normal values are
less than 100 mg/ml, recent studies suggest a
higher threshold may be required (i.e., around
250 mg/ml) in order to discriminate heart
failure dyspnea from other causes in the ICU
(Principi et al., 2009; Rana et al., 2006).
Bhardwaj and Januzzi (2009) illustrate a more
detailed diagnostic and monitoring algorithm
for acute heart failure utilizing BNP.
The higher the levels of BNP, the more severe is
the heart failure. In fact, increases in BNP ≥ 75
pg/ml at 24 h after ICU admission carry a
threefold increased likelihood that the patient
will require intubation (Vander Werf et al.,
2010).
However, serial values closer than 48–72 h
apart during an individual hospitalization are
not recommended because BNP levels to do not
decrease
consistently
after
treatment.
Decreased renal clearance, a common
occurrence in critically ill patients, may also
influence values to remain elevated, thus
limiting the BNP’s diagnostic value (Rana et al.,
2006). BNP has been found to be superior to
clinical judgment for diagnosing acute
decompensated heart failure and, in one trial,
was able to improve diagnostic accuracy from
209
74 to 81% (Bhardwaj and Januzzi, 2009), and
because of this, BNP testing has been associated
with improvments of length of stay in hospital
(Hunt et al., 2009; Lam et al., 2010). If
diagnosed, treatment for acute heart failure
may include the following:
Oxygen
BiPAP (decreases work of breathing, lowering
myocardial oxygen demand, and decreases
preload by increasing intrathoracic pressure
and pressure to the inferior vena cava, thus
lowering venous return)
Morphine IVP (decreases afterload, preload,
and perceived shortness of breath)
Lasix (decreases preload)
Nitroglycerin (if hypertensive, to decrease
preload and afterload)
Clincians must also be aware of noncardiac
causes of BNP elevation, such as acute
pulmonary embolism, pulmonary hypertension,
septic
shock,
hyperthyroidism,
renal
insufficiency, and advanced liver disease
(Bhardwaj and Januzzi, 2009; Hunt et al.,
2009).
210
Clinical Pearls
When patients with a history of heart failure
are thought to have hypovolemic shock
(systolic blood pressure (SBP) <90 mmHg),
aggressive fluid resuscitation to perfuse end
organs must be strongly considered while
measures to support airway and breathing
are simultaneously undertaken.
Conclusions
Pulmonary management of critically ill adults is
a mainstay of monitoring and treatment in
critically ill patients. While considerable
research has been conducted in mechanically
ventilated patients, significant difficulties arise
in researching patient conditions that are
widely heterogeneous. Monitoring protocols for
early detection and safety have been reviewed
in this chapter but further research is needed to
establish evidence-based guidelines for optimal
care and outcomes.
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222
Chapter 4
Electrocardiographic
monitoring for
cardiovascular dysfunction
Catherine Winkler
Fairfield University, Fairfield, CT., USA
Cardiovascular disease is the leading cause of
mortality and morbidity in the United States
accounting for approximately 33.6% of deaths
annually (Xu et al., 2010). Although death rates
from cardiovascular disease (CVD) have
declined in recent years, the overall burden of
the disease remains very high. Heart disease is
more common among people aged 65 and
older; however, the onset of heart disease in
younger individuals is gradually becoming more
prevalent. More than 150 000 Americans who
died because of CVD in 2007 were less than 65
years old (Xu et al., 2010). In addition, more
than 61.8 million people currently live with
CVD, which can be a major cause of disability
producing
more
than
2.1
million
hospitalizations each year (Center for Disease
Control and Monitoring, 2010). The cost of
expenditure on heart disease in 2010 was
$316.4 billion (Xu et al., 2010). Heart disease
expenditure estimates include hospitalizations,
223
procedures, physician visits, medications, and
lost productivity. Accordingly, cardiovascular
admissions continue to predominate in the
intensive care unit (ICU) and in the step-down
units where advanced practice registered nurses
(APRNs) will encounter electrocardiographic
(ECG) monitoring as an important component
of clinical care.
Physiologic guidelines
The control of risk factors for CVD such as
hypertension,
hyperlipidemia,
smoking,
diabetes, obesity, and lack of physical activity
remain a central issue for many Americans.
Data from the National Health and Nutrition
Examination Survey Center for Disease Control
and Monitoring, 2010 indicate that 30.5% of US
adults (≥20 years of age) have hypertension and
that 15% of US adults have elevated cholesterol
levels (≥240 mg/dl). Furthermore, despite 40
years of smoking cessation recommendations,
in 2009, among Americans (≥18 years of age),
23.1% of men and 18.3% of women continued to
be cigarette smokers (Lloyd-Jones et al., 2010).
Regrettably, Americans diagnosed with diabetes
mellitus represent 8.0% of the adult population
and this number is rising, along with an
astonishing estimated prevalence of obesity in
US adults (≥20 years of age) of 68% in 2008
(NHANES, 2008). These factors along with
36% of Americans who report that they do not
engage in any physical activity (Lloyd-Jones et
224
al., 2010) present a challenge for nurse
practitioners who are engaged in population
health initiatives. Frequently, patients with
heart disease have more than two of these risk
factors and other comorbidities such as kidney
disease and respiratory illnesses. These
associated conditions further complicate
treatment and present a conundrum to
hospitals and all health-care providers who are
struggling to provide preventive care as well as
treat diseases in a cost-effective manner.
Many hospitals meet the challenge of triaging
acute cardiovascular hospitalizations through
the development of alternative care settings.
Settings such as chest pain centers, observation
units, post-anesthesia recovery, or intermediate
care units together with the traditional
inpatient units, telemetry, step-down, and
intensive care try to deliver the right care to the
right patient at the right time in the right locale.
The delivery of cost-effective, high-quality care
to patients with heart disease is conducted by
ensuring that core measures are met in the
inpatient setting, that the patient experience is
constructive with education and medication
reconciliation provided, and that outcomes are
optimized. Likewise, one of the ways that
high-quality efficient care can be achieved is
through “targeted” ECG monitoring that is
determined by the surveillance needs of the
patient. Surveillance in this context involves a
review of the practice standards for ECG
225
monitoring (Drew et al., 2004) and other
related evidence-based literature, following
criteria as determined by the practice setting
with established ECG monitoring levels, and
defining the monitoring goals based on the
patient’s clinical needs. ECG monitoring can
range from simple heart rate and basic rhythm
interpretation to complex cardiac arrhythmias,
myocardial
ischemia,
and
prolonged
QT-interval surveillance (Drew et al., 2004).
Goals of monitoring
Targeted or patient-centric ECG monitoring is
best applied when an immediate assessment of
the patient is made to determine the level of
optimal monitoring. Based on the diagnosis on
admission and changes in the patient’s clinical
condition during hospitalization, ongoing
medical decisions are predicated on the
interventions and specific goals of care. The
rating system devised by the American College
of Cardiology Emergency Cardiac Care
Committee (Jaffe et al., 1991) includes three
categories: class I cardiac monitoring is
indicated for all patients within the group (post
cardiac arrest, acute coronary syndrome, etc.);
class II monitoring may be beneficial for some
patients but not essential for all (syncope, post
myocardial infarction [MI], etc.); and class III
monitoring in which monitoring has no
therapeutic benefits (permanent rate-controlled
atrial fibrillation [AF]). After a decision is made
226
regarding the category of ECG monitoring and
the level of intensity that is required for a
patient, the specific inpatient setting is selected
as well as a plan for the monitoring timeframe.
ECG monitoring is one of the most important
tools to diagnose cardiac disease and alterations
associated with changing health status.
Therefore, important clinical decisions such as
the medication therapy, device adjustments
(e.g., pacemaker and implantable cardioverter
defibrillator [ICD]), further diagnostic testing,
cardiac consultation, unit transfers, and length
of stay are made every day using ECG
monitoring data. The American Heart
Association (AHA) practice standards (Drew et
al., 2004) provide direction for ECG monitoring
that will assist APRNs in deciding which
patients are best served by ECG monitoring
during an episode of care. Equally important to
realize is the power of misdiagnosis of the ECG
monitoring data that can result in adverse
patient outcomes from undertreatment to
selection of the wrong therapy. Recognizing
artifacts and other pitfalls resulting from
patient
movement,
outside
electrical
interference, and misplaced electrodes and
leads will ultimately result in improved patient
outcomes (Baranchuk et al., 2009). Registered
nurses must establish the proper location and
the correct preparation for electrode placement
for proper ECG monitoring and ongoing
comparison of rhythm strips over time.
227
APRNs and expert staff nurses are central in
deciding on the goals of monitoring for an
individual patient as they are in the best
position to detect clinical problems early to
mitigate them to optimize patient outcomes. A
patient is monitored for a variety of reasons: to
detect changes in a patient’s clinical condition,
to diagnose a problem, to assess a response to
an intervention, to prevent an undesirable
event, and for surveillance before and after
surgery. Through an understanding of the
patient’s underlying health-care issues and the
pathology, the nurse can select the leads that
will supply the best and most clinically
significant information.
To provide optimum care and establish
appropriate ECG monitoring, it is important to
review the cardiac diseases that are clinically
managed using this technology. Indications for
ECG monitoring include the following
conditions: post successful cardiopulmonary
resuscitation; acute coronary syndrome (ACS);
cardiac arrhythmias; heart failure; electrolyte
abnormalities; critical illnesses; and drug
overdose (if there is a potential pro-arrhythmic
complication) (Drew et al., 2004; Jevon, 2010).
All of these clinical diagnoses need ECG
monitoring to exam and assess for cardiac
dysfunction. Nurse practitioners are in a
position to assist in setting the standards for
ECG monitoring in their facility through their
recommendations and leadership.
228
Post cardiopulmonary resuscitation
The purpose of ECG monitoring in the early
days of coronary care units was the immediate
recognition of cardiac arrest. However, it was
quickly realized that nurses needed not only to
identify and respond to cardiac arrest but also
to detect life-threatening arrhythmias to
decrease mortality in patients who had an acute
MI (Webner, 2011). From this time forward
with the technological improvements in ECG
surveillance, it was understood that cardiac
arrhythmias could result in hemodynamic
instability and sudden cardiac death (Webner,
2011). Education of staff involved in arrhythmia
detection of emergent arrhythmias such as
asystole and ventricular tachycardia include
bradycardias, heart blocks, and both wide and
narrow complex tachycardias. Beyond early
recognition and response to cardiac arrest,
nurses
are
now
charged
with
post-cardiopulmonary resuscitation support,
which requires continuous assessment of
physiological
parameters
through
hemodynamic monitoring, recognition of
typical complications (MI, adult respiratory
distress syndrome, deep vein thrombosis,
pulmonary emboli), and timely interventions.
Patients resuscitated from cardiac arrest should
be a top priority for monitoring until the
reversible cause such as hyperkalemia is
corrected or until an ICD is implanted. Acute
coronary syndrome is a common cause of
229
cardiac arrest; subsequently, the clinician needs
to evaluate the patient’s 12-lead ECG and
cardiac biomarkers (see Table 4.1). As a result
of a high incidence of ischemia, aggressive
treatment of ST-elevation MI needs to begin
immediately along with emergent percutaneous
coronary intervention (PCI) in the context of
concurrent ongoing life support.
Table 4.1 Biomarkers used for diagnosis of
acute MI.
Test
Estimated Sensitivity Description
peak (h) and
specificity
Troponin 12
Subunits
Tn1, TnT
↑↑↑
sensitivity
and
specificity
Troponin is
released with
the
degradation
of actin and
myosin
filaments.
Released in
2–4 h/
persists for
up to 7 days
Creatine 10–24
kinase or
CK-MB
↑↑ relatively
specific
when
skeletal
muscle
CK-MB
facilitates
movement of
high-energy
phosphates
into and out
230
Test
Estimated Sensitivity Description
peak (h) and
specificity
damage is
absent
of
mitochondria.
It is in many
types of
tissues even
in the skeletal
muscle. Short
duration; it
cannot be
used for late
diagnosis of
acute MI but
can be used to
suggest
infarct
extension if
levels rise
again.
Normal
within 2–3
days
CK-MB, creatine kinase–myocardial band; h,
hours; MI, myocardial infarction.
Monitoring elements
It is important to identify the essential
post-resuscitation clinical problems of the
patient before deciding on monitoring needs.
231
Patients who continue to be hemodynamically
unstable will require monitoring for arrhythmia
detection and ongoing ischemia. Depending on
the cause of the cardiac arrest and the
medications that the patient had been taking,
even QT-interval prolongation may be an
ongoing concern that will require surveillance.
Clinicians need to recognize ECG changes
indicative of impending torsades de pointes and
implement interventions to prevent this and
subsequent cardiac arrest (Sommargren and
Drew, 2007).
Evidence-based treatment guidelines
The guidelines published by the American
College of Cardiology [ACC] (Jaffe et al., 1991)
and practice standards (Drew and Funk, 2004)
recommend monitoring the patient until
hemodynamically stable and the clinical
problem is corrected. The primary reasons for
bedside cardiac monitoring include arrhythmia
detection,
ST-segment
monitoring,
and
QT-interval monitoring as identified by Drew
and colleagues (2004), and they may all apply
to the patient who is recovering from cardiac
arrest. The best lead for monitoring
arrhythmias is V1; the next best is V6. Use of V1
allows the practitioner to more easily view P
waves, differentiate left and right bundle
branch blocks, and distinguish ventricular from
supraventricular rhythms with aberrant
conduction (Kumar, 2008). Monitoring for
232
ST-segment changes will allow for rapid
intervention and leads III and V3 are
recommended by the American Association of
Critical Care Nurses (AACN) if the involved
coronary arteries are unknown (Bourgault,
2009). If the patient has a prior history of
ischemia, then it is best to monitor the patient
in a more directed way in the leads that reflect
the vessels involved in the ischemic event (see
Table 4.2). Prolongation of the QT-interval can
also occur because of a genetic predisposition
or through acquired abnormalities such as renal
failure and acute pancreatitis. In the acute care
setting, often the etiology for QT-interval
prolongation is related to medications such as
some
antibiotics,
antipsychotics,
and
antiarrhythmics (Sommargren and Drew,
2007). Patients in this situation would need to
be monitored for QT-interval prolongation until
the medication is discontinued or dosage
established with no lengthening of the QTc. The
QTc is considered prolonged when it is greater
than 0.47 s in males and greater than 0.48 s in
females. If the QTc is greater than 0.50 s in
anyone, it can be associated with higher risk for
torsades de pointes (Moss, 1999).
233
Clinical Pearls—Patient
Management and Treatment
Survival rates at discharge for patients who
experience in-hospital cardiac arrest are only
27% among children and 18% among adults
(Lloyd-Jones et al., 2010). The National
Registry for Cardiopulmonary Resuscitation
in 2007 identified that for the events
reported, 93% were monitored or witnessed
and that ventricular fibrillation or pulseless
ventricular tachycardia was listed as the first
recorded rhythm (Lloyd-Jones et al., 2010).
Continuous cardiac monitoring for recurrent
arrhythmias, ST-segment monitoring for
ongoing ischemia, and tracking the
QT-interval in patients with known clinical
risk factors are important elements for
hemodynamic optimization and
multidisciplinary goal-directed therapy
protocols to improve survival (Gaieski et al.,
2009).
Table 4.2 Monitoring
vessels, and selected leads.
234
recommendations,
Type of
Coronary Lead selection
monitoring vessel
involved
Arrhythmia
monitoring
LAD
V1—intraventricular
septum
Primary lead
Arrhythmia
monitoring
Left
V6—lateral wall
circumflex
Secondary
lead
Ischemia
monitoring
LAD
V3—anterior wall
Ischemia
monitoring
RCA
Ischemia
monitoring
Left
V5 and V6—lateral
circumflex wall
V1, V 2, V 4
III—inferior wall
II, aVF
I, aVL—sometimes
no change
V1, V2, or V3 for
reciprocal changes
posterior wall
If ischemic
footprint
unknown
LAD and
RCA
Demand
ischemia
Left
V5—lateral wall
circumflex
235
V3 and
III—anterior and
inferior leads
Type of
Coronary Lead selection
monitoring vessel
involved
QT-interval
monitoring
N/A
Monitor in the lead
with best-defined T
wave
LAD, left anterior descending; RCA, right
coronary artery.
Acute coronary syndromes
In 2006, when primary and secondary
discharge diagnoses were considered together,
there were 1 365 000 unique hospitalizations
for ACS, of which 765 000 were male and 600
000 were female (National Hospital Discharge
Survey, 2008). Patients in the early phases of
ACS such as ST-elevation/non-ST-elevation MI,
unstable angina, or rule-out MI should be
monitored for a minimum of 24 h for an
uncomplicated MI or for at least 24 h after
complications (e.g., ongoing chest pain) have
resolved (Drew et al., 2004). For patients who
are experiencing ACS or a rule-out MI
diagnosis, monitoring will involve a greater
intensity based on the admission diagnosis.
Levels of monitoring intensity are established
based on best practice recommendations, which
are generated from AHA published standards
(2004) and Jaffe and colleagues (1991). Those
patients who have an acute MI can be at risk for
236
reperfusion arrhythmias with the incidence of
7.5% after an infarct (Al-Khatib et al., 2002).
Furthermore, patients with elevated troponin
levels compared to those patients with normal
levels are more likely to develop arrhythmias
after PCI (Bonnemeier et al., 2003). These
patients should be monitored for 12–24 h
because of the possibility of an abrupt closure.
Early revascularization does not guarantee
optimal myocardial perfusion in patients
undergoing primary angioplasty. In some
patients, perfusion remains impaired and
therefore identifying worsening ST-segment
elevation post PCI is critically important (Aude
and Mehta, 2006). In general, stenting the
artery has provided patients with less frequent
reocclusions post procedure. Patients receiving
thrombolytic therapy for an acute MI should be
monitored for at least 12–24 h if event-free to
assure that the culprit artery remains patent.
Lastly, patients with a potential for vasospasm
(Prinzmetal angina, cocaine) should be
monitored for ST-segment changes until after
therapy is initiated or till they are event-free for
12–24 h. Patients who do not have an
arrhythmia may have ECG monitoring
discontinued unless they have enduring
ST-segment changes and QT-interval deviations
that require continuous monitoring. Sometimes
there are practical limitations to using
ST-segment monitoring such as when a patient
is
physically
restless.
Under
these
circumstances, ST-segment monitoring may not
237
be possible because of fluctuating changes in
the baseline ECG pattern. There are several
methods to improve ST-segment monitoring to
include early identification of body position
changes on the monitor and recorded strips to
serve as a reference. Nurses should also adjust
the alarm parameters for the individual patient
once the baseline is established, and carefully
prepare the electrode site placing the leads in
the proper location. Establishing a reference
point for the ST-segment, adjusting the alarm
range, and securing the electrodes will all help
to minimize false alarms while still providing
cardiac monitoring for those patients who are
restless.
Monitoring for ST-segment changes is
important for those at risk for myocardial
ischemia including patients who have unstable
angina, chest pain, or post-op patients with a
history of heart disease as well as those in
critical care who may have a primary diagnosis
other than cardiac but are at risk for demand
ischemia. It is imperative to differentiate
ischemia from infarction. Ischemia is caused by
a reduction in blood supply, resulting in less
oxygen delivered to a region of the heart. ECG
changes during an ischemic event are
represented by contiguous T wave inversions
and/or ST-segment depression. ST-segments
that are 1 mm or more below baseline following
the J-point or where the QRS complex meets
the T wave are considered to be ischemic.
238
Infarction develops when there is prolonged
ischemia leading to myocardial necrosis.
Infarction can be diagnosed by ST segments
that will elevate ≥1 mm in limb leads and
≥2 mm in chest leads representing the earliest
signs of an evolving MI. Prompt intervention
may prevent myocardial injury and infarction.
As referenced in the practice standards,
biphasic T waves in leads V2 and V3 could
represent Wellen’s sign (Drew et al., 2004). It is
a critical finding because it is associated with
significant stenosis of the left anterior
descending coronary artery and may be
indicative of an MI.
Monitoring ST-segments can be challenging;
therefore, a baseline must be established with
the patient in a supine position. If the patient
moves or changes positions, it can cause
ST-segment variations and false alarms as
referenced earlier. The key to minimizing false
alarms is to set alarm parameters accurately
and monitor for trends in the ST segment. If
one does not know the pattern of changes in ST
segments because prior ischemic changes were
not noted and the coronary arteries involved
are unknown, then it is best to select leads III
and
V3
per
AACN
recommendations
(Bourgault, 2009). However, lead V5 is the best
for monitoring demand ischemia. The problem
with monitoring in just one lead is that as much
as 50% of the ST-segment depression events
may be missed in a single lead configuration;
239
therefore, multiple-lead monitoring provides
the greatest coverage for ischemic changes
(Booker et al., 2003) and should be used
whenever possible. Booker and colleagues
(2003) report that demand ischemia may be
transient in noncontiguous leads without the
patient experiencing symptoms. Patients with
these conditions, as well as the availability of
fibrinolytic therapy and PCI, have contributed
to the change in focus for continuous cardiac
monitoring from just arrhythmia detection to
ischemia monitoring as well. Oversight of
ST-segment changes is important not only to
assess and treat patients with known heart
disease but also to protect patients who either
experience silent or unreported ischemia (Drew
and Krucoff, 1999) and for those who are at risk
for reocclusion of target vessels after PCI.
Monitoring elements
Arrhythmia monitoring is compulsory because
ischemia and infarction may cause lethal
arrhythmias. In addition to arrhythmia
monitoring,
patients
with
ACS
need
surveillance because ST-segment elevation is an
independent predictor of mortality, even after
controlling for multiple clinical factors (Langer
et al., 1998). These patients have top priority
because of ongoing ischemia that may result in
an acute MI or an extension of an MI. As
referenced earlier, the toughest decision with
patients who have ACS is the selection of the
240
best lead to monitor for ST-segment pattern
changes. The inherent risk is that the wrong
choice will result in missing an evolving event.
It is important to note that a left bundle branch
block or pacemaker-dependent rhythms
present challenges to the diagnosis of acute
ischemia because of alterations in the QRS
complex and T wave that obscure typical
ischemic changes. To aid in a definitive
diagnosis of acute MI, it is best, when possible,
to contrast the new pattern with an old ECG.
This will help to determine if a preexisting left
bundle branch block had presented before the
acute event. With a new-onset left bundle
branch block, the recommendations are to
determine if the new bundle with ST-segment
elevation of 1 mm or more is concordant with
the QRS complex; if the ST-segment depression
of 1 mm or more is present in lead V1, V2, or V3;
and if ST-segment elevation of 5 mm or more is
discordant from the QRS complex in the
right-sided leads (Wackers, 1987). Lastly,
pericarditis, which is an acute inflammation of
the pericardium, can cause both PR depressions
and ST-segment elevations during the patient’s
initial presentation to the hospital. Through
this acute phase of pericarditis, the
ST-elevations are usually diffuse throughout the
precordial and limb leads in a nonanatomic
distribution (Wang, Asinger, and Marriott,
2003), differentiating it from an acute MI
241
presentation. Once treated, all ECG changes
will return to baseline.
Evidence-based treatment guidelines
Research supports continuous ST-segment
monitoring to enable the practitioner to
monitor all potential ischemic zones (Drew and
Krucoff, 1999; Johnson, 2008; Leeper, 2007).
The
2004
Practice
Standards
for
Electrocardiographic Monitoring in Hospital
Settings provides the “best practice” for
continuous ECG monitoring based on expert
opinion (Drew et al., 2004). The consensus
guidelines outline ECG indicators (in the
absence of left ventricular hypertrophy and left
bundle branch block) as new ST-segment
elevations at the J-point in two contiguous
leads with the cutoff of more than 2 mm in men
and 1.5 mm in women in leads V1 and V2 and/
or more than 1 mm in the other leads. The
guidelines also describe acute myocardial
ischemia as ST-segment depression of greater
than 0.5 mm in two contiguous leads and/or T
wave inversion greater than 1 mm in two
contiguous leads with a prominent R wave
(Sandau and Smith, 2009). Over 20 years ago,
Krucoff and colleagues (1988) initially
described ST-segment monitoring as helpful to
identify recurrent myocardial ischemia after MI
or PCI. In a randomized controlled trial of 424
patients presenting to the emergency
department with chest pain, researchers used
242
ST-segment monitoring as one component of
their protocol during the patient’s stay in the
chest pain center. They found that it was
influential as a cost-effective alternative to
hospital admission for those patients with an
intermediate risk of unstable angina (Farkouh
et al., 1998). In another study, Gibler and
associates (2005) found that half of the patients
with
acute
coronary
syndrome
who
demonstrated ST-segment depression on the
initial 12-lead ECG went on to have an MI
within hours. However, even with these early
studies as well as ongoing evidenced-based
experience, ST-segment monitoring outside the
catheterization lab has been slow in translating
into practice.
Selection of the appropriate lead is the key to
accurate bedside monitoring. Each lead reflects
the electrical activity in a specific region of the
heart and the corresponding vessel that
supplies it (Table 4.2). Changes that occur in
one or more leads will help the practitioner
identify the vessel(s) and region of the heart
that are likely affected by ischemia or
infarction. Patients with a right coronary artery
occlusion, which supplies the inferior wall of
the left ventricle, should be monitored in leads
II, III, and aVF. It is important to keep in mind
that lead II will display the least significant
change. Anterior wall infarctions are usually
associated with occlusions of the left anterior
descending branch of the left coronary artery,
243
for which, subsequently, the best leads are V3
and V4. For the intraventricular septum, leads
V1 and V2 are well matched for detecting
ischemic changes in the septal region. The
lateral wall infarctions are usually associated
with occlusion of the left circumflex artery and
in one-third of cases there are no visible
changes. When ischemic changes do occur in a
patient, they are visualized in leads I, aVL, V5,
and V6. Reciprocal depression ST-segment
changes will occur in leads V1, V2, and V3 when
there is a posterior infarction or posterior leads
may be applied (Fig. 4.1).
Clinical Pearls—Patient
Management and Treatment
It is also important to note that ST-segment
monitoring may need to be specifically
ordered if it is not automatically turned on
when a patient is attached to the system.
Although most cardiac monitors have
computerized ischemia monitoring, often the
nurse must activate it in order to have it
monitor for ST-segment changes. Unlike
computerized arrhythmia monitoring, which
is automated, ST-segment ischemia
monitoring must often be manually turned
on (Drew et al., 2004). Unfortunately,
computerized ischemia monitoring is still
244
underused in the acute care setting (Funk et
al., 2010). It is not clear why both
ST-segment and QT-interval prolongation
are undermonitored but according to Funk
and colleagues (2010), it may be related to
lack of knowledge on the part of nurses and/
or the absence of physician support for the
practice. Anecdotally, some physicians
believe that the incidence of reocclusions
post procedure is so low because of stent use
that ST-segment monitoring is not as
important as it might have been in the earlier
days of PCI. Funk and colleagues (2009)
observe that for over 50 years continuous
ECG monitoring has been primarily focused
on arrhythmia detection. In fact, some
hospitals with old ECG-monitoring
equipment only have arrhythmia monitoring.
However, ST-segment does have a place in
clinical care and ST-segment monitoring
should be applied to provide surveillance not
only to those with acute MI but also to
patients who experience demand ischemia or
have silent ischemia without symptoms.
ST-segment alarms should be set for 1 mm
above and below baseline when monitoring
in V1 or V6. Alarm limits can be set tighter
with the limb leads using parameters set at
0.5 mm above and below the baseline
(Webner, 2011). In contrast, for
245
post-coronary artery bypass graft (CABG)
patients, leads may need to be set with a
wider range to accommodate the associated
ST-segment changes that may occur due to
perioperative inflammation. The
recommendation is to monitor the
ST-segments 1.5 mm above and below the
patient’s baseline during the postsurgical
phase of recovery. If continuous 12-lead
monitoring is unavailable in the acute phase
of illness, a 6-lead telemetry system should
be used to monitor V1 for arrhythmias and
the second V lead for detection of ischemia. It
is important to note that, for patients who
have intermittent ventricular pacing with
ST/T wave abnormalities, a left bundle
branch block, or an intermittent right bundle
branch block, continuous ST-segment
monitoring is not recommended because
these rhythm patterns will trigger false
alarms (Drew et al., 2004). A special
consideration is the identification of the
patient who has a right ventricular infarct.
This can occur in the context of an inferior
wall MI and it is imperative that it is
recognized because nitrates are
contraindicated, whereas they are typically
used in the management of most other types
of MI (Calder, 2008). In addition to ST
elevations in II, III, and aVF to definitively
diagnose a right ventricular infarct, it is
246
essential to move chest leads V3 through V6
from the usual left side of the chest to the
right. If a right ventricular infarct is present,
ST elevations will appear in the right-sided
V4 (Garvey et al., 2006) and may also be
present in additional RV leads. Another
circumstance is when a posterior infarction is
suspected because of ST depressions in V1,
V2, and V3 with large R waves. A posterior
ECG can be obtained by repositioning leads
V4 through V6 (Fig. 4.2). The V4 lead is
placed on the left posterior axillary line, V5 at
the border of the left scapula, and V6 near the
vertebrae, to note any ST elevations (Garvey
et al., 2006).
247
Figure 4.1 Posterior V7–V9 placement.
From Morris and Brady (2002). © BMJ.
Figure 4.2 Electrode placement for right
ventricular and posterior infarction detection.
248
Cardiac arrhythmias
Published literature such as the practice
standards for ECG monitoring (Drew et al.,
2004) and the practice alert on dysrhythmia
monitoring (Bourgault, 2009) require a patient
to be monitored when there is a significant risk
for life-threatening arrhythmias, specifically
ventricular tachycardia, ventricular fibrillation,
and asystole. Drew and colleagues (2004)
recognize that nurses have the lead
responsibility in attaching the ECG monitor and
screening true from false alarms, documenting
the onset and termination of tachyarrhythmias,
and recording rhythm strips from the atrial
epicardial pacemaker in patients who have had
cardiac surgery. As discussed under the
headings of post cardiac arrest and acute
coronary syndrome, patients who have been
resuscitated and/or have unstable coronary
syndromes and newly diagnosed high-risk
coronary lesions are at high risk for
arrhythmias. Interventions such as early
revascularization,
beta-blockers,
nitrates,
angiotensin-converting enzyme inhibitors, and
other antiplatelet and antithrombotic agents
have decreased the incidence and time course of
problematic arrhythmias (Drew et al., 2004).
Similarly, ECG monitoring data from 278
patients with acute coronary syndrome who
participated in a larger prospective study
evaluating myocardial ischemia were found to
have fewer life-threatening arrhythmias, but
249
experienced frequent benign premature
ventricular
contractions
(PVCs)
and
nonsustained ventricular tachycardia (Winkler
et al., 2013). Frequent PVCs and other serious
ventricular ectopy may be a marker for more
severe heart disease; however, they are not
independent predictors of adverse outcomes.
ECG monitoring needs to be established for
only those individuals who are at risk for
significant arrhythmias as outlined in the
practice standards rather than for those who
have benign or chronic arrhythmias. Patients
who have undergone angioplasty, experience a
complication in the catheterization lab, or have
an inconclusive outcome should also be
monitored for 24 h or longer if arrhythmias
have occurred. When the intra-aortic balloon
pump is used to support cardiac function,
arrhythmia recognition and tracking may be
difficult because of changes in the overall ECG
pattern. Generally, tracking arrhythmias is
central to patient care to sort out and review
only those arrhythmias that contribute to a
decrease in effectiveness of the heart.
Patients who have undergone cardiac surgery
should be monitored for 48–72 h or longer,
possibly until discharge, if they are at high risk
for developing AF according to the practice
standards (Drew et al., 2004). The risk factors
for post-op AF include advanced age, past
history of AF, valve disease, and in those with a
preoperative hold of beta-blockers. Patients
250
who undergo structural heart procedures such
as valvuloplasty, transcatheter aortic valve
replacement, and atrial septal closure devices as
well as those who have the mini-maze
procedure should also be monitored for
arrhythmias for 12–24 h and longer as
warranted based on the clinical course.
Another category of patients who need ECG
monitoring are those who have a temporary or
new device such as an ICD or pacemaker
implanted
during
their
course
of
hospitalization. For example, a patient with a
temporary pacemaker or transcutaneous pacing
pads has a short-term set of connections where
lead or pad dislodgement is possible.
Oversensing or loss of capture could easily
occur necessitating an immediate intervention.
This is especially important if the patient is
device-dependent. Similarly, patients with AV
block who are, or could easily become,
hemodynamically
unstable
need
ECG
monitoring until the block either resolves or
definitive treatment (ICD or pacemaker) is
implemented.
Wolf–Parkinson White syndrome is associated
with sudden cardiac death. Usually during AF,
there is fast anterograde conduction over the
accessory pathway and so patients need to be
carefully monitored until they can be treated,
often with an ablation. Torsades de pointes is a
life-threatening arrhythmia that is associated
251
with long QT syndrome and PVCs that might
trigger this arrhythmia, which could degenerate
into ventricular fibrillation. Therefore, intensive
ECG monitoring is clinically indicated until the
patient can be stabilized. Any other
life-threatening arrhythmias, especially in those
patients
with
heart
disease
where
hemodynamic instability is likely, should be
monitored until the cause is determined and
treated.
Monitoring elements
The expected practice is to select the best
monitoring lead for the patient based on the
type of arrhythmia that the patient has or is
suspected to develop during their inpatient
stay. Lead V1 is the best to distinguish
ventricular tachycardia from supraventricular
tachycardia
with
aberrant
conduction,
recognize atrial activity, and differentiate
between left and right bundle branch blocks
with lead V6 as a second choice (Johnson,
2008).
Evidence-based treatment guidelines
The practice standards for ECG monitoring in
the hospital setting (Drew et al., 2004) outline
the three classes of arrhythmia monitoring.
Class I indications have been listed for post
cardiac arrest, acute coronary syndrome, after
cardiac
surgery,
nonurgent
PCI
with
252
complications, device implants, temporary
pacemaker, and transcutaneous pacing, and
those with AV block, Wolf–Parkinson White,
and long QT syndrome. In addition, patients
who are on the intraaortic balloon pump, with
acute heart failure/pulmonary edema, with any
hemodynamically unstable arrhythmia, in the
ICU, or undergoing conscious sedation should
be monitored for arrhythmias. Those patients
who are post acute MI, with chest pain
syndromes, have undergone uncomplicated,
nonurgent PCI, and who require adjustments of
medications
to
control
the
rate
of
tachyarrhythmias, all fall into class II
monitoring, where this may benefit only some
patients. Additionally, patients who are also
classified as group II for ECG monitoring
include those who undergo pacemaker lead
replacement but are not pacemaker-dependent,
uncomplicated ablation of an arrhythmia,
routine diagnostic cardiac catheterization,
subacute heart failure, syncope evaluation, and
lastly, those who are terminally ill but have an
arrhythmia that is uncomfortable with
symptoms of palpitations and shortness of
breath that require arrhythmia management
(Drew et al., 2004). There are patients who,
although they may be very ill, fit into class III
where they do not require ECG monitoring
because they are at very low risk for an
occurrence.
Patients
who
undergo
uncomplicated
surgical
procedures,
hemodialysis, and patients with stable
253
arrhythmias such as rate-controlled AF or the
occasional PVCs in the absence of a moderating
condition such as electrolyte abnormality or
myocardial ischemia are all in class III (see
Table 4.3).
Clinical Pearls—Patient
Management and Treatment
Patients who have the potential for a
prolonged QTc measurement not only have
top priority for QT-interval monitoring but
also for arrhythmia monitoring. Patients who
have been started on a QT-prolonging
medication have a primary diagnosis of an
overdose from a potentially pro-arrhythmic
medication, a heart rate of less than 40
beats/min or a pause of over 2 seconds
severe hypokalemia, or hypomagnesemia are
also candidates for monitoring. They should
be observed until the underlying disorder is
corrected, the offending drug is discontinued,
or the potentially pro-arrhythmic dosage is
established with no prolonged QTc. There is
no definitive threshold with QT prolongation.
However, a QTc beyond 0.50 ms is
considered precariously extended, increasing
the risk for torsades de pointes, a rare
polymorphic ventricular tachycardia (Rodin,
2008). An interesting finding in a study by
Pickham and colleagues (2010) is that
254
women received a greater proportion of
QT-prolonging drugs, had more frequent
electrolyte disturbances, and experienced a
greater risk for QT interval prolongation and,
consequently, torsades de pointes than men.
Since QTc prolongation develops over hours,
constant measurement is not necessary.
However, when possible, a baseline QTc
measurement should be followed and
recalculated every 8–12 h. It is also best to
measure the QTc in the same lead by
calculating the length of the QT-interval in
seconds and then correcting it for heart rate.
Some ECG monitors have electronic calipers
available; otherwise, a manual calculation of
the QTc is required. The most common
QT-interval calculation formula in use was
introduced by Bazett (1920) and many
monitoring systems have this formula
automatically embedded in monitoring
software. The six antiarrhythmic drugs that
are especially likely to cause QT prolongation
include disopyramide, dofetilide, ibutilide,
procainamide, quinidine, and sotalol (Drew
et al., 2004).
Table 4.3 ECG
classifications.
monitoring
255
arrhythmia
Class I
Class II
Class III
Highest risk
Moderate risk
Low risk/
ECG
monitoring
not required
Post cardiac
arrest
Post acute myocardial Postoperative
infarction
uncomplicated
surgical
procedures
Acute coronary
syndrome
Chest pain syndromes Hemodialysis
Postoperative
cardiac surgery
Uncomplicated,
nonurgent PCI
Stable
arrhythmias
such as
rate-controlled
atrial
fibrillation
Nonurgent PCI
with
complications
Tachyarrhythmias
requiring medication
adjustments
Occasional
PVCs in the
absence of a
moderating
condition such
as electrolyte
abnormality or
myocardial
ischemia
Device implants
Pacemaker lead
placement and not
pacemaker-dependent
256
Class I
Class II
Class III
Highest risk
Moderate risk
Low risk/
ECG
monitoring
not required
Temporary
pacemaker and
transcutaneous
pacing
Uncomplicated
ablation of
arrhythmias
AV block
Routine, diagnostic
catheterization
Wolf–Parkinson
White
Subacute heart failure
Long QT
syndrome
Syncope
Intra-aortic
balloon pump
Terminally ill with
arrhythmia, which
causes palpitations or
SOB and requires
management
Acute heart
failure/
pulmonary edema
Hemodynamically
unstable
arrhythmia
In intensive care
257
Class I
Class II
Class III
Highest risk
Moderate risk
Low risk/
ECG
monitoring
not required
Undergoing
conscious
sedation
AV,
atrial-ventricular;
electrocardiographic;
PCI,
coronary intervention.
ECG,
percutaneous
Acute heart failure
Arrhythmias such as AF that have an associated
rapid ventricular rate can either cause or result
from acute decompensated heart failure.
Patients with acute heart failure or pulmonary
edema should have arrhythmia monitoring
until the signs/symptoms of acute heart failure
have resolved and no hemodynamically
significant arrhythmias occur for 24 h (Drew
and Funk, 2006). Patients with stable heart
failure admitted for rate control through
medication titration should be monitored on
telemetry to determine drug efficacy. Those
with severe heart failure who require inotropic
drugs that have pro-arrhythmic properties (e.g.,
dobutamine, milrinone) or are having infusion
rate adjustments also need ECG monitoring.
Additionally, patients with heart failure with a
258
recent history of revascularization should be
monitored in V1 for arrhythmia detection and
another V lead for ischemia monitoring. Those
with subacute or mild heart failure can benefit
from ECG monitoring although in a prospective
analysis of the utility of telemetry monitoring in
711 patients, medical decisions for this patient
population were guided by cardiac monitoring
only 17% of the time (Opasich et al., 2000).
Even though telemetry monitoring in this study
played a weaker role than expected, the authors
speculated that perhaps cardiac monitoring
provided patients and physicians with
reassurance of the success of the therapeutic
approach and in some instances might have had
an
effect
on
avoiding
inappropriate
interventions. Kumar (2008) also observed that
criteria were established using admission
diagnosis with monitoring recommended for
24–72 h for patients with heart or respiratory
failure who experienced syncope. Patients who
have acute heart failure requiring admission to
the ICU should be monitored until
hemodynamically stable. In non-ICU patients,
monitoring should continue for a period of
24–72 h for heart failure patients who also
experience syncope or other comorbidities,
which make them more vulnerable for
arrhythmias. Conditions such as post-op
revascularization, ongoing ischemia, or rhythm
disturbances are examples that warrant
continuation of ECG monitoring.
259
Monitoring elements
Continuous ECG monitoring for patients with
acute heart failure is justified to watch for
new-onset arrhythmias in lead V1 and when
medication or device (ICD, pacemaker) therapy
is being adjusted (Drew et al., 2004) since sinus
tachycardia is often a normal physiological
response to acute decompensated heart failure.
Drugs such as inotropic agents and vasodilators
used to treat heart failure can also exacerbate
sinus tachycardia and may be arrhythmogenic.
Although there are many cardiac and
noncardiac causes of AF, it is very common in
patients who have heart failure. Consequently,
the incidence of AF increases with the
progression of clinical heart failure (Naccarelli
et al., 2003). In the absence of randomized
clinical trials, it is still prudent to monitor
patients in the subacute phase of heart failure
while medications, device therapy, or both are
being manipulated.
Clinical Pearls—Patient
Management and Treatment
The most common reasons for readmissions
are when the ICD has fired in a patient who
experiences ventricular arrhythmias (61%)
and progressive heart failure (13%) (Kapoor,
2002). Therefore, it is reasonable to monitor
260
the patient while an ICD is interrogated or
through the time frame needed to correct the
underlying cause of the defibrillator firing
and after having alleviated heart failure
symptoms.
Electrolyte abnormalities
Electrolyte
abnormalities
of
potassium,
calcium, and magnesium have been associated
with life-threatening arrhythmias. Conditions
in which there is a depletion of electrolytes after
cardiac surgery, or lowered electrolyte values
occurring due to a variceal bleed treated with
vasopressin, or after receiving massive blood
transfusion may potentiate the incidence of
tachyarrhythmias in these very ill patients.
Inadequate levels of potassium, calcium, and
magnesium can prolong the QT-interval, which
can increase the risk of ventricular arrhythmias
and cardiac arrest. Hyperkalemia is sometimes
seen in patients with renal insufficiency or in
patients who take angiotensin-converting
enzyme inhibitors. Elevated potassium levels
may increase myocardial excitability and impair
the conduction system (Kahloon et al., 2005).
Low potassium levels may also cause
arrhythmias, especially in patients with
underlying heart disease and those with digoxin
toxicity (Hoes et al., 1994). Hypomagnesemia
and hypocalcemia, especially in the setting of
261
other risk factors, can lead to prolongation of
the QT-interval. Electrolytes need to be
carefully monitored and treated as needed in all
patients, especially those with underlying
disease.
Monitoring elements
Patients need to be monitored for as long as
they are symptomatic with either arrhythmias
or QT-interval prolongation. Once they are
hemodynamically stable and the underlying
condition is treated, ECG monitoring may be
discontinued.
Evidence-based treatment guidelines
There are no specific evidence-based guidelines
other than the AHA practice standards that list
electrolytes as a high potential risk factor for
the generation of arrhythmias or prolongation
of the QT-interval (Drew et al., 2004).
Clinical Pearls—Patient
Management and Treatment
Patients who are experiencing electrolyte
abnormalities should be monitored while
their levels are corrected through an
intervention although there is no
recommended threshold for monitoring
patients in the absence of ECG deviations.
262
ECG abnormalities typically occur when the
potassium level exceeds 6.5 mmol/l, but
normal ECGs (particularly in renal failure
patients) have been reported in patients with
potassium levels above 9.0 mmol/l (Szerlip,
Weiss, and Singer, 1986).
Critical illnesses
Continuous
ECG
monitoring
is
a
recommendation for patients who are critically
ill under a class I category for cardiac
monitoring. Patients admitted to the ICU with
major trauma, respiratory failure, sepsis, shock,
pulmonary embolus, a major noncardiac
surgery (especially in elders with a history of
coronary artery disease or who have cardiac risk
factors), renal failure with electrolyte
abnormalities as referenced earlier or drug
overdose as listed later, and other serious
illnesses should be monitored with the length of
time determined by the specific clinical
condition (Drew et al., 2004). In addition,
patients whose respiratory failure is linked to
hypoxemia, hypercapnea, or uncompensated
respiratory acidosis should be considered for
ECG monitoring secondary to the risk of
arrhythmias as well as patients who have
suffered an ischemic or hemorrhagic stroke
(Kumar, 2008). Patients who are ill enough to
be admitted to the ICU may require all three
263
types of cardiac monitoring: arrhythmia,
ST-segment, and QT-interval, depending on the
etiology of their condition. Class II cardiac
monitoring is suggested for patients with acute
neurological
events
like
subarachnoid
hemorrhage who are prone to QT prolongation
even though according to Sommargren and
colleagues (2002) these patients usually do not
develop torsades de pointes.
Monitoring elements
Careful consideration should be given to the
subset of patients with critical illnesses who,
although do not meet the AHA practice
standards for ECG monitoring (Drew et al.,
2004) in some instances, may warrant
surveillance based on the severity of their
illness and the goals of their care.
Evidence-based treatment guidelines
The AHA guidelines do not include some
noncardiac conditions where there may be good
evidence to provide ECG monitoring. One area
of consideration for cardiac monitoring is for
those patients who require massive blood
transfusions defined as replacing the person’s
entire blood volume within 24 h (Chen and
Hollander,
2007).
Hypocalcemia
and
hypomagnesemia (both from citrate toxicity)
could develop in patients who require massive
amounts of blood. In one study by Wilson and
colleagues (1992), patients with hypocalcemia
264
experienced mortality rates of 71% compared to
those with normal calcium levels whose
morality rate was 41%. Even though
hypomagnesemia alone is unlikely to cause
arrhythmias, it is thought to potentiate the
effect of coexisting hypocalcemia (Meikle and
Milne,
2000).
Patients
who
have
gastrointestinal hemorrhage after endoscopy
may benefit from ECG monitoring because
life-threatening
arrhythmias
have
been
reported in the literature (Eden, Teirstein, and
Weiner, 1983; Faigel, Mets, and Kochman,
1995; Mauro et al., 1988). Torsades de pointes
could occur in patients who have had
neuroleptic medication during the procedure
and QT prolongation has occurred with
intravenous vasopressin, especially when
patients have other electrolyte abnormalities
(Faigel, Mets, and Kochman, 1995).
Clinical Pearls—Patient
Management and Treatment
Expert staff and APRNs are positioned to use
ECG monitoring based on the patient’s
underlying pathophysiology. Hospitalized
patients who are often older adults with
comorbidities should be assessed hourly with
the clinical indications for ECG monitoring
applied when indicated.
265
Drug overdose
Patients with an overdose or drug toxicity
without an arrhythmia should be monitored for
24–48 h, and longer if there is an arrhythmia or
a high potential for one to develop. As
referenced under the arrhythmia section,
certain drugs, particularly those that have a risk
for prolonged QT-interval and, subsequently,
torsades de pointes, require heightened
surveillance of the patient for possible
problems. Concurrently, if the patient has other
risk factors including older age, history of heart
disease, low ejection fraction, or acquired or
genetic predisposition to QT prolongation,
these conditions may predispose the patient to
an untoward outcome. A drug overdose of
known arrhythmogenics such as digitalis,
tricyclic antidepressants, phenothiazines, and
narcotics as well as polypharmacy use
exponentially increases the likelihood of an
adverse event (see also Chapter 13).
Monitoring elements
It is important to be aware of the side effects
and interactions of all medications to avoid a
poor outcome. Optimal management is possible
when medications can be fully reconciled by the
APRN or nurse while educating the patient.
266
Evidenced-based guidelines
There are no specific guidelines for ECG
monitoring of patients with drug overdose other
than the recommendations put forth by the
AHA in the practice standards for ECG
monitoring (Drew et al., 2004).
Clinical Pearls—Management
and Training
Drug overdose can be purposeful or
accidental due to the high number of
medications that patients take and the
complexities of their illness. Polypharmacy or
taking more than five medications along with
coexisting risk factors and illnesses in the
context of complex drug regimens
contributes to noncompliance as well as
adverse drug reactions. It is estimated that
patients who are prescribed 10 or more
medications have over a 90% chance of
experiencing one or more clinically
significant adverse events (Nolan and
O’Malley, 1988). Twenty years later this
problem continues because patients are
prescribed many medications that interact
adversely and/or the side effects often go
unrecognized. APRNs and registered nurses
are instrumental in medication reconciliation
267
and education to preempt potential adverse
outcomes.
Unnecessary arrhythmia
monitoring and underutilization of
ischemia and QT-interval
monitoring
Almost as important as understanding when a
patient requires ECG monitoring is recognizing
when they do not. Unnecessary monitoring
increases health-care costs, diverts nursing and
medical staff from other important work, and
may give patients an incorrect message about
the status of their cardiac health. It is vital,
especially in today’s health-care environment,
to apply the ECG-monitoring practice standards
(Drew et al., 2004). Based on expert opinion,
these standards assist in delineating resources
for specific conditions and assure that they are
not overutilized and instead are applied
efficiently to care that is appropriate.
Sometimes physicians use monitored beds for
patients who might only require frequent
observation and nursing care. When systematic,
rigorous standards for inpatient telemetry
admissions are not applied, monitored beds
quickly become inaccessible and patients are
forced to remain in emergency settings or for
prolonged stays in post-anesthesia areas. These
268
decisions contribute to overcrowding or ICU
delayed transfers, potentially increasing length
of stay.
Conversely, Funk and colleagues (2010) found
that undermonitoring for ischemia and QTc
prolongation
occurred
frequently
in
hospitalized patients. In the analysis of baseline
data from their randomized clinical trial
(PULSE), the authors found that, of the patients
with an indication for ischemia monitoring,
only 35% of patients were being monitored, but
26% with no indication were monitored for
ST-segment changes. Likewise, only 21% of
patients with an indication for QTc monitoring
had a QTc documented while 18% with no
indication for QTc had it documented.
Undoubtedly, as technology advances, ECG
monitoring and human oversight of the patient
remains indispensable, the criteria of evolving
clinical models of care must be frequently
reexamined through cost-effectiveness research
with the aim to deliver the right type and dose
of cardiac monitoring.
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278
Chapter 5
Hemodynamic monitoring in
critical care
Kathy J. Booker
School of Nursing,
Decatur, IL., USA
Millikin
University,
Hemodynamic monitoring
overview
Rapid assessment techniques develop with
experience and are critical in the surveillance of
all patients admitted to intensive care unit
(ICU)
settings.
Combining
continuous
electrocardiographic data with hemodynamic
assessments
provides
minute-to-minute
assessment data that must be analyzed
carefully. In this chapter, monitoring systems
that inform care providers about the impact of
the hemodynamic status of critically ill adults
will be reviewed.
Mathews
(2007)
broadly
defined
hemodynamics as the forces involved with
blood circulation. Functional hemodynamic
monitoring has been defined as “that aspect of
the measure of cardiovascular variables, either
alone or in response to a physiologic
perturbation, that defines a pathophysiological
279
state, drives therapy or identifies cardiovascular
insufficiency more accurately and often earlier
than possible by analysis of static hemodynamic
variables” (Hadian and Pinsky, 2007, p. 318).
The evolution of hemodynamic monitoring
from static variables to those capable of
trending continuous fluctuations in stroke
volume (SV) and cardiac output (CO) has
changed the landscape of hemodynamic
monitoring over the past decade. The
application of less invasive techniques to more
accurately predict volume responsiveness offers
considerable advantages although systems still
remain fallible, especially in patients with
spontaneous breathing or cardiac rhythm
irregularities.
Understanding
hemodynamic
monitoring
requires
both
a
foundation
in
pressure-detection systems used extensively
over the last four decades and newer
technologies based on fluid responsiveness and
SV
indices,
still
under
investigation.
Increasingly, research is focused on patient
outcomes of hemodynamic monitoring systems.
Over the past decade, direct arterial pressure
waveform analysis and other hemodynamic
variables have been studied using monitoring
devices that are less invasive than pulmonary
artery catheters (PACs). Stroke volume
variation (SVV) and CO calculated from arterial
pressure systems have emerged as accurate
methods for trending hemodynamic status
280
although research has been equivocal and
newer systems are not applicable in all critically
ill patients (Bendjelid and Romand, 2003;
Berkenstadt et al., 2001; Cannesson et al., 2011;
Liu et al., 2010; Marik et al., 2009; Wiesenack
et al., 2003). Liu et al. (2010) found SVV,
monitored by peripheral arterial lines, to be
accurate indicators of cardiac preload and CO.
Marik et al. (2009) conducted a systematic
review on arterial waveform variables and fluid
responsiveness in mechanically ventilated
patients,
concluding
that
arterial
pressure–derived
estimates
of
volume
responsiveness yielded higher accuracy when
compared with static measures. Although
arterial-derived variables to assess fluid
responsiveness have been found to be reliable
in a number of studies, many factors influence
reliable measurement and most studies have
been done with patients on controlled
mechanical ventilation to control for cardiac
conditions affected by changing intrathoracic
pressure (Marik et al., 2009). As new
technology has emerged, parameters that can
be monitored or calculated have changed
considerably. Terms and normal values
associated with hemodynamic monitoring are
reviewed in Table 5.1.
Table 5.1 Terms associated with hemodynamic
monitoring.
281
Adapted from Baird and Bethel (2011);
Cannesson et al. (2011); Napoli (2012).
Term
Definition
Normal
values
Arterial
The pressure
115/75
pressure (AP) exerted on the
walls of blood
vessels by
circulating
blood ejected
into the arterial
circulation
Arterial
oxygen
saturation
The saturation 95–98%
of oxygen on
the hemoglobin
molecule;
represents the
majority of
delivered
oxygen to
tissues
Arteriovenous
oxygen
content
difference
(C[a − v]O2)
The difference
between
arterial and
venous O2
content,
refelecting
oxygen supply
and demand:
CaO2 × CvO2
282
4–6 ml/vol%
Term
Definition
Normal
values
Cardiac index Cardiac output 2.5–3.5
(CI)
divided by
l/min/m2
body surface
area
Cardiac
output (CO)
Amount of
blood ejected
from the
ventricles per
minute
4–6 l/min
Central
venous
pressure
(CVP)
Pressure
measured in
the thoracic
vena cava
representing
cardiac filling
pressure or
preload of the
RV
2–6 mmHg
Left
ventricular
stroke work
index
(LVSWI)
SVI (MAP −
PAOP) ×
0.0136
40–75
Mixed central
venous
saturation
(ScvO2)
Venous
60–80%
admixture of
venous blood
returned to the
RA;
283
g/m2/beat
Term
Definition
Normal
values
approximates
SvO2 but does
not include the
venous return
from the
coronary
circulation
Mixed venous
oxygen
saturation
(SvO2)
Venous
60–80%
admixture
oxygenation
status once all
venous blood
has been
returned to the
RV (CO × CaO2
× 10) − VO2
Oxygen
Body usage of
consumption available
oxygen
delivered to
tissues,
calculated by
CO × 10 × C(a
− VO2)
200–250 ml/
min
Oxygen
delivery
(DO2)
800–1000 ml/
min
Arterial
delivery of
oxygen to
tissues
284
Term
Definition
Normal
values
factoring
arterial oxygen
content and
CO: CaO2 × CO
× 10
Passive leg
A test used to
raising (PLR) estimate fluid
responsiveness,
conducted by
raising the legs
passively,
subsequently
causing an
estimated
300–500 ml
venous return
to the heart,
mimicking
fluid
administration.
Used to assess
improvements
in vital signs
and tissue
oxygenation
induced by
additional
preload
285
Fluid
responsiveness
to PLR is
measured by
change in CO/
CI or stroke
volume >
10–15%
Term
Definition
Normal
values
Pulmonary
artery
pressure
(PAP)
Pressure
20–30/8–15
exerted by
mmHg
blood flow in
the pulmonary
artery
Pulmonary
artery
occlusive
pressure
(PAOP)
Pressure
6–12 mmHg
measured
when a
balloon-tipped
PAC is inflated
and floats into
an occlusive
branch of the
pulmonary
artery; reflects
forward
pressure from
left atrium and
LV assuming
no mitral valve
dysfunction
Pulse
Systolic blood <40 mmHg
pressure (PP) pressure −
diastolic blood
pressure,
reflective of
arterial wall
stiffness
286
Term
Definition
Normal
values
Pulse
pressure
variation
(PPV)
A calculated
measure of
pulse variation
using arterial
or pulse
oximetry pulse
variation to
estimate fluid
responsiveness
expressed as a
percentage
improvement.
Calculated as a
percentage:
PPV = 100 ×
(PPmax −
PPmin)
[(PPmax +
PPmin)/2]
PPV > 13–15%
has been
associated with
fluid
responsiveness
in mechanically
ventilated
critically ill
patients
(Napoli, 2012)
Right atrial
pressure
(RAP)
Pressure
4–6 mmHg
measured
within the right
atrium of the
heart
Right
ventricular
stroke work
index
SVI (PAM −
4–8 g/m2/beat
RAP) × 0.0136
287
Term
Definition
Normal
values
Stroke
volume (SV)
Volume of
blood ejected
from ventricles
with each
cardiac
contraction
50–70 ml/beat
indexed to
patient’s size
(stroke volume
index [SVI]):
SV/body
surface area
Stroke
volume
variation
(SVV)
A measure
taken from the
arterial
pressure curve
in newer
noninvasive
hemodynamic
systems;
affected by
intrathoracic
pressure
changes and
cardiac
arrhythmias;
research
supported only
in mechanically
ventilated
patients.
Possibly less
affected by
SVV varies
based on
patient
populations:
9.5% predictive
in neurosurgery
patients;
10–13% in
other surgical
populations.
288
Term
Definition
Normal
values
vasomotor tone
(Napoli, 2012).
Calculated by
arterial
pressure
systems and
displayed as a
percentage:
Venous
oxygen
content
(CvO2)
These
percentages are
indicators of
predicted
positive
response to
fluid
administration
(preload
responsiveness)
Venous oxygen 15.5 ml/vol%
content
following tissue
level
extraction: Hgb
× 1.34 × SvO2
The multitude of developing hemodynamic
systems has created confusion, particularly due
to variation in systems, limited study findings
on diverse critical care patient conditions, and
variable outcome end points (Vincent et al.,
2011). See Table 5.2 for key elements of
hemodynamic monitoring systems advanced by
Vincent et al. (2011). Various hemodynamic
monitoring systems will be reviewed within this
chapter.
289
Table 5.2
monitoring.
Principles
of
hemodynamic
Adapted from Vincent et al. (2011). © BioMed
Central, Ltd.
1
No hemodynamic monitoring technique
can improve outcomes by itself.
2
Monitoring requirements may vary over
time and can depend on local equipment
availability and training.
3
There are no optimal hemodynamic values
that are applicable to all patients.
4 We need to combine and integrate
variables.
5
Measurements of SvO2 can be helpful.
6 A high cardiac output and a high SvO2 are
not always best.
7
Cardiac output is estimated, not measured.
8 Monitoring hemodynamic changes over
short periods of time is important.
9 Continuous measurement of all
hemodynamic variables is preferable.
10 Non-invasiveness is not the only issue.
290
Hemodynamic monitoring
systems
Pulmonary artery catheter monitoring
PACs have been used since the 1970s following
the development of the PAC by Drs. Swan and
Ganz (Rajaram et al., 2013). Following
widespread adoption of this catheter as a
monitoring tool for critically ill patients,
clinicians and researchers began to question its
use, noting less-than-optimal outcomes and
potential deleterious complications in patients
(Harvey et al., 2005; Manoach, Weingart, and
Charchaflieh, 2012). Despite a long history of
PAC use in critical care units, evidence has
demonstrated limited application due to risks
associated
with
placement,
potential
complications, weak clinical outcomes, and
considerable user error (Harvey et al., 2010;
Isakow and Schuster, 2007; Manoach,
Weingart, and Charchaflieh, 2012; NHLBI
ARDS, 2006).
PACs are inserted through a central vein
(generally the subclavian or internal jugular)
and advanced through the right atrium, right
ventricle, and into the pulmonary artery (PA;
see Fig. 5.1). The PAC ports allow for multiple
blood sampling, monitoring of right heart and
PA pressures, and are equipped with an
inflatable balloon at the distal tip to allow for
brief PA occlusion to obtain intermittent
291
pressures reflective of left ventricular
end-diastolic pressure (LVEDP). Theoretically,
with normal mitral valve function, the
pulmonary artery occlusive pressure (PAOP)
aligns with LVEDP at end expiration and, often,
PA diastolic pressures are similar to LVEDP.
Problems with distal tip positioning, mitral
valve insufficiency or stenosis, ventricular
compliance, and technical issues may all affect
the accurate measurement of PAOP. In
addition, pressure does not equate to volume
and allows for only estimations of volume
status. Intermittant or continuous cardiac
output (CCO) monitoring is possible using a
PAC.
Figure 5.1 Waveforms during insertion of
pulmonary artery catheters.
From Baird and Bethel (2011, p. 90). © Elsevier.
292
Specially developed PACs also allow for
continuous monitoring of mixed venous
oxygenation (SvO2). Table 5.3 reviews factors
affecting SvO2.While CCO values and SvO2
provide significant information on overall
hemodynamic status and systemic oxygenation,
newer methods add significantly to decisions
regarding fluid volume responsiveness. Preload,
afterload, and contractility measures are often
computed from values obtained by PACs in an
effort to optimize hemodynamic status.
Standard PAC monitoring may be used more
frequently in patients with severe known
cardiac disease or conditions in which trending
continuous SvO2 is helpful.
Table 5.3 Factors affecting SvO2.
Baird & Bethel (2011). Manual of Critical Care
Nursing. Elsevier.
Svo2 is a sensitive indicator of oxygen supply/
demand balance, If Svo2 decreases to less than
50%, the patient should be rapidly assessed for
the cause of an increased oxygen demand, or
decrease in supply. Anemia, hypoxemia, and
decreased CO may result in markedly reduced
oxygen delivery. In the presence of the high
metabolic demands imposed by critical illness,
a reduction in O2 delivery or further increase
in O2 demand can produce profound
instability in the patient. Changes in Svo2
293
often precede overt changes reflective of
physiologic instability.
Factor
Effect Clinical Examples
on
Svo2
Arterial Oxygen Saturation
↑ Sao2
↑ Svo2 Supplemental oxygen
↓ Sao2
↓Svo2 Reduced oxygen supply
(e.g., ARDS, ET
suctioning, removal of
supplemental oxygen,
pulmonary disease,
asthma, respiratory
failure, obstructive sleep
apnea)
Cardiac Output
↑CO
↑Svo2 Administration of
inotropes to increase
contractility
↓CO
↓Svo2 Dysrhythmias, increased
SVR, MI, hypovolemia,
↑HR, or ↓HR
Hemoglobin
↓Hgb
↓Svo2 Hemorrhage, hemolysis,
severe anemia in patients
with cardiovascular
disease
Oxygen Consumption
294
↑Vo2
↓Svo2 States in which metabolic
demand exceeds oxygen
supply (e.g., shivering,
seizures, hyperthermia,
hyperdynamic states)
↓Vo2
↑Svo2 States in which there is
failure of peripheral tissue
to extract or use oxygen:
Significant peripheral
arteriovenous shunting:
cirrhosis, renal failure
Redistribution of blood
away from beds where
oxygen extraction occurs:
sepsis, acute pancreatitis,
major burns
Blockage of oxygen uptake
or utilization: cyanide
poisoning (including
nitroprusside toxicity),
carbon monoxide
poisoning
Mechanical ↑Svo2 Wedged PA catheter
Problems
creates falsely elevated
Svo2
ARDS, acute respiratory distress syndrome; CO,
cardiac output; ET, endotracheal; Hgb,
hemoglobin; MI, myocardial infarction; PA,
pulmonary artery; SVR, systemic vascular
resistance.
295
Nursing management and care of patients with
PACs is considerable. Following insertion, ports
may be used for administration of multiple
intravenous fluids, blood products, and blood
sampling. When not in use, ports must be
maintained with flush protocols to prevent
clotting
at
blood/port
interfaces
and
management of sterility at the insertion site
requires considerable attention to prevent
central line infections. PACs are inserted
through a separate introducer catheter, which
must also be managed. When proximal ports
are used for central venous pressure (CVP)
monitoring and the distal port used for PA
pressure monitoring, pressurized sterile
systems must be maintained and monitored
frequently during the shift. Derived values from
a PAC are generally obtained every 4 h and
continuous or intermittent CO measures are
also trended. While monitoring frequency is
guided by orders or standing protocols,
outcome studies have not clearly linked
monitoring to improved outcomes (Rajaram et
al., 2013).
Central venous pressure monitoring and
management
The use of central venous catheters (CVCs) to
support hemodynamic management is common
in the ICU. Central lines serve a number of
purposes including multiple infusion ports for
incompatible solutions, delivery of fluids at
296
higher flow rates than peripheral catheters,
monitoring and trending CVP, use for
short-term dialysis, and the ability to trend
central venous blood for oxygenation and
laboratory analysis. While monitoring CVP as a
measure of preload is generally inaccurate due
to the wide range of physiological conditions
that influence values, many other indications
for CVCs in critically ill patients continue
(Marik, Baram, and Vahid, 2008). Factors that
may influence changes in compliance or volume
in the central veins include changes in CO,
peripheral venous constriction, position
changes, arterial dilation, blood or fluid loss
through trauma, hyperthermia, hypothermia,
conditions that engage the Valsalva maneuver,
muscle contraction, and exertion. While still a
central component of sepsis guidelines, CVP
monitoring is generally not used to guide
therapy, especially with the emergence of other
hemodynamic techniques offering greater
hemodynamic precision. However, the role of
CVCs in newer systems for SVV will be explored
later in this chapter.
Central venous pressure trending
limitations
Marik, Baram, and Vahid (2008) conducted a
classic systematic review and identified the
inaccuracies of the CVP as an indicator of
intravascular volume, noting that CVP values
were no better than chance in estimating fluid
297
responsiveness. Other studies have identified
collapse of the superior vena cava during
positive pressure ventilation when CVP is less
than 10 mmHg (Jellinek et al., 2000;
Viellard-Baron et al., 2003), technically
invalidating its predictive value.
Osman et al. (2007) found that cardiac filling
pressures were not helpful in predicting fluid
responsiveness in patients with sepsis. Neither
CVP nor PAOP predicted fluid responsiveness
even when low stroke volume index (SVI)
values were known. Use of CVP trending is
more valuable than individual assessments and
may be used along with other hemodynamic
parameters to supplement assessment rather
than independently used as a driver for
therapeutic intervention.
Arterial line monitoring and
management
Arterial lines are frequently inserted in critically
ill adults to monitor continuous blood pressure
and allow frequent arterial sampling for
trending arterial blood gas analysis, especially
in patients on mechanical ventilation.
Increasingly, arterial lines are also used for
functional hemodynamic monitoring. As a
vascular access device, arterial line systems
require special pressurized tubing and
monitoring systems that include a transducer
and continuous waveform analysis for safe
298
application and trending. Guidelines for
management and monitoring of arterial lines
have been published (Kunde, 2012). High-level
(I and II) supportive recommendations for
management identify that arterial catheters do
not require routine changing although these
catheters should not be overlooked when
assessing for infectious sources; flush systems
do not require heparin for thrombi prevention;
and general safety of arterial lines is
established, noting less than 1% major
complications (Kunde, 2012). Actual frequency
of monitoring and documentation are not
addressed in this guideline although the
recommendation of checking all connections at
the beginning of each shift is emphasized. In
critically ill patients, the use of arterial pressure
systems requires heightened surveillance due to
the very rapid blood loss and risk for
exsanguination associated with dislodgement or
tubing disconnection. Alarms should be
enabled at all times to alert nursing staff to
changes in arterial pressure and waveforms
displayed continuously to aid in the
surveillance of this technology.
Newer techniques for SVV measurement and
management use arterial waveform analysis to
calculate SV. Combined with CVP-derived
measures of central venous oxygenation,
adequacy of hemodynamic states may be
trended. Bridges (2008) reviewed functional
hemodynamic studies that have contributed to
299
critical care practice using arterial-based
systems, highlighting the paucity of outcome
studies and identifying the numerous
limitations in the accuracy of systems, including
respiratory
variation
in
spontaneously
breathing patients, dynamic responsiveness of
systems, calibration issues, and uncertainty in
cutoff points for management decisions based
on SVV and systolic pressure variation (SPV).
These variables will be further explored.
Hemodynamic monitoring
guidelines and outcomes
Hemodynamic monitoring must be linked to
treatments that improve patient outcomes
(Garcia and Pinsky, 2011; Napoli, 2012; Pinsky,
2007; Pinksy and Payen, 2005). All monitoring
systems reviewed earlier may place patients at
additional infectious and functional risk, a
common critique of traditional PA monitoring
systems. Harvey et al. (2005) observed that
approximately 10% of over 500 critically ill
patients randomized to PAC use developed
complications, including hematoma at the
insertion site, arterial punctures, arrhythmias
requiring treatment, and pnemothoraces. No
differences in mortality or length of stay were
observed in the PAC versus non-PAC groups.
Similar complications and frequency were
noted in a comparison study of trauma patients
in
which
PAC
versus
transthoracic
300
ultrasonography outcomes were compared
(Tchorz et al., 2012). In the National Heart,
Lung, and Blood Institute clinical trials network
for adult respiratory distress syndrome (ARDS)
(2006), comparisons of CVC-guided treatments
versus PACs in 1000 patients detected fewer
complications in the CVC group with no
improvement in patient outcomes with the use
of PACs (NHLBI ARDS, 2006). The
recommendations from this network include
abandonment of the use of PACs for patients
with acute lung injury monitoring.
The goal in all hemodynamic monitoring is to
allow for trend analysis and evaluation of
interventional techniques to prevent and treat
tissue
hypoperfusion.
Prevention
of
deterioration and measureable hemodynamic
improvement in critically ill patients are key
goals of critical care management in the ICU.
While newer techniques often involve
placement of arterial catheters and central
venous lines, these are considered less invasive
forms of hemodynamic monitoring compared
with the use of PACs. Many newer techniques
based on SV responsiveness also have
limitations in that ventricular function is not
directly trended (Marik et al., 2009) and due to
inaccurate arterial waveform analysis in
patients with arrhythmias such as atrial
fibrillation. Indeed, in the monitoring
guidelines for patients in shock, Antonelli et al.
(2007) observed that CO monitoring lacks a
301
gold standard and is not recommended as a
routine measurement in patients with shock.
See Chapter 2 for further synopsis of these
guidelines in patients with shock conditions.
Nursing
surveillance
is
required
for
hemodynamic monitoring and patient safety,
management of hemodynamic variables, and
appropriate functioning of systems to ensure
data accuracy.
Functional indicators of hemodynamic
monitoring
Types of functional monitoring that have been
validated through research include volume
challenge, passive leg raising, changes in CVP
during spontaneous breathing, and changes in
left ventricular output during positive pressure
ventilation (Pinksy and Payen, 2005). The
cornerstone of newer hemodynamic techniques
is the ability to assess fluid responsiveness,
identified “as an increase of 10–15% in stroke
volume (SV), cardiac output (CO), or cardiac
index (CI) in response to volume expansion”
(Napoli, 2012, p. 2). Early goal-directed therapy
(EGDT) is foundational to the preservation of
hemodynamic stability at early stages of clinical
deterioration, particularly in sepsis (Antonelli
et al., 2007; Rivers et al., 2012). A review of
outcome studies over a decade following the
introduction of EGDT and sepsis bundles, in
over 18 000 adult patients, concluded that
EGDT significantly reduced mortality and
302
progressive organ failure, health-care costs, and
inflammatory response (Rivers et al., 2012).
Nursing is key to implementation of EGDT
protocols and most emergency and critical care
units have adopted sepsis initiatives (see
Chapter 2).
Perioperative optimization
Perioperative hemodynamic optimization has
been studied extensively. The use of blood
pressure as a guide for hemodynamic status is
misleading due to the many factors affecting
blood flow and pressure. Generally, complex
and interactive factors affect vascular flow and
tissue oxygenation, altered significantly during
surgery, perioperative recovery, and in many
critical conditions requiring ICU stays.
Interventions to ensure adequate tissue oxygen
delivery
(DO2)
intraoperatively
using
goal-directed fluid therapy have been effective
(Kirov, Kuzkov, and Moinar, 2010). Blood
pressure and heart rate often mask
hypovolemia in perioperative and critically ill
patients. Compensatory mechanisms to sustain
CO
involve
increased
heart
rate,
vasoconstriction, and increased peripheral
oxygen extraction. Blood pressure reductions
are considered a late sign, accompanied by poor
organ perfusion and reduced urinary output.
Prevention of this cascade is always the goal.
303
Transesophageal monitoring
Esophageal Doppler techniques estimate SV
and CO more directly through Doppler
technology. Transesophageal Doppler (TED)
techniques evaluate fluid challenges and patient
responsiveness to circulatory volume challenges
and have been studied extensively in surgical
patients. The technique and equipment used in
TED
are
simpler
than
transthoracic
echocardiography but generally require that
patients be sedated. The probe is inserted orally
or nasally and advanced to the midthoracic
region where the esophagus and the descending
aorta are aligned. Adjustments are made in the
calculation of blood flow since the distribution
is generally 70% in the descending aorta and
proprietary factoring of patient age, weight,
height, and aortic cross-sectional area is
converted to estimates of SV and CO (Schober,
Loer, and Schwarte, 2009).
Phan et al. (2008) reviewed perioperative fluid
optimization with TED in a meta-analysis of
nine randomized controlled studies. In this
analysis, patients had reduced lengths of stay,
improved return of gastrointestinal function (in
colorectal surgery patients), and reduced
postoperative morbidity compared with
controls who did not have fluid management by
TED. Phan et al. (2008) promote the use of 250
ml boluses of colloids to treat low SVV.
Parameters that are trended with TED include
304
preload width (FTc), representing systolic flow
time; peak velocity, reflective of contractility;
and SVI. These continuously displayed values
are analyzed following fluid boluses, with 10%
improvement in SVV desired. When patients
have less than 10% improvement, preload
optimization is evidenced and further fluids are
not indicated. Other trended values obtainable
by esophageal Doppler methods include CO,
preload, afterload, and left ventricular
contractility (Vincent et al., 2011).
The Agency for Healthcare Research and
Quality (2007) issued a technology assessment
on the use of TED and endorsed the
effectiveness of this technology to guide fluid
replacement during surgery with decreased
surgical complications when compared with
CVP monitoring, assigning strong evidence to
these findings. While the insertion of the probe
used to monitor TED and additional education
to interpret data obtained by TED are
necessary, this technique in critical care units
holds promise for positively influencing critical
care treatment and outcomes.
Volume responsiveness
While fluid challenges are often a first-line
treatment for hemodynamic instability, the
measurement of fluid responsiveness is often
difficult given physiologic interactions within
the
thorax,
compliance
issues,
and
compensatory
circulatory
action.
305
Approximately half of unstable critically ill
patients will respond to a fluid challenge
(Marik, Baram, and Vahid, 2008; Marik et al.,
2009; Michard and Teboul, 2002). The key to
successful fluid responsiveness is optimizing
fluid volume in patients whose ventricular
function is responsive to fluids (on the
ascending portion of the Frank–Starling curve),
maximizing SV with additional fluids.
Successful optimization of goal-directed fluid
therapy is especially effective using Doppler
technology in high-risk surgical patients
(Roche, Miller, and Gan, 2009).
Marik et al. (2009) found strong correlation of
pulse pressure variation (PPV), SVV, and SPV
changes on stroke index/CI values in a
systematic review of dynamic changes in
arterial waveform-derived variables. In 29
pooled studies, PPV performed the best in
response to fluid challenge on the outcome
variable, with 0.94 correlation and 0.94 area
under the curve (p < 0.001). While these
measures reflect volume responsiveness,
clinicians must keep in mind the limitations of
this technique, particularly the invalidation of
calculations
in
patients
with
cardiac
arrhythmias
and
variable
spontaneous
breathing patterns that influence venous return
to the heart. In addition, the status of left
ventricular function is not revealed by this
technique so its application is limited to those
306
with recruitable preload conditions (Marik et
al., 2009).
PPV is directly calculated by most arterial
pressure-based systems by averaging the
maximal pulse pressure minus the minimum
pulse pressure divided by the average of these
two (Wiesenack et al., 2003). As a reflection of
left ventricular stroke work, the PPV is less
influenced by intrathoracic pressure changes.
Manoach, Weingart, and Charchaflieh (2012)
reviewed the current literature on invasive
monitoring and volume responsiveness during
resuscitation, perioperative management, and
in critical care. Manoach, Weingart, and
Charchaflieh (2012) concluded that use of PAC
may be helpful in patients with a number of
conditions, including complex right and left
cardiopulmonary
disorders,
pulmonary
hypertension, and selected complex cardiac
surgery, trauma, and high-risk surgical
patients. Recommendations for application of
CVP-based systems were supported in critically
ill patients with left-sided heart failure, septic
shock, ARDS and other subsets of critically ill
patients
(Manoach,
Weingart,
and
Charchaflieh, 2012). Finally, arterial pulse
pressure trending is recommended in patients
in sinus rhythm with sufficient sedation to
offset mechanically ventilated intrathoracic
effects on venous return (Δ PP). Since
spontaneous breathing lessens the predictive
307
value of Δ PP to fluid responsiveness, and
arrhythmias also invalidate values, the
limitations in the use of these systems are
evident. Manoach, Weingart, and Charchaflieh
(2012) highlight many of the serious
complexities
inherent
in
managing
hemodynamic monitoring in critically ill
settings.
While many of the techniques for assessing
fluid responsiveness are not accurate in
spontaneously breathing patients, pulse
oximetry plethysmography analysis may hold
promise.
Plethysmography
analysis
in
anesthetized, controlled ventilation patients
revealed that changes in pulse oximetry
waveforms (Δ POP) were predictive of fluid
responsiveness (Desebbe and Cannesson;
Wyffels et al., 2007). Changes in pulse oximetry
waveforms (Δ POP) may be predictive of fluid
responsiveness, enabling noninvasive trending
of hemodynamic changes, but continued
research is needed (Cannesson et al., 2011).
Pulse contour analysis
Arterial waveform pulse contour analysis is a
technique used for hemodynamic monitoring in
critical care. Some systems on the market use a
derivation based on pulsatile analysis from
existing arterial pressure waveforms. Others
use combined data obtained from CVC and
arterial
pressure
monitoring,
applying
algorithms to analyze pulse contours and
308
intermittent thermodilution measures to derive
CO. When combined with a CVC, these systems
also allow for measurement of central venous
oxygenation (ScvO2) and left ventricular SV
estimated by measurement of arterial pulse
pressure, CCO, and SV. The magnitude of
changes in the pulse pressure is reflective of
changing SV affected by arterial compliance. A
key element of this technology is the ability to
evaluate responses to fluid challenge. Garcia
and Pinsky (2011) noted that “volume
responsiveness has been arbitrarily defined as ≥
15% change in cardiac output in response to a
500 ml bolus fluid challenge” (p. 1) but
cautioned that this is but one element of
evaluating critically ill patients. Using measures
of SV and oxygenation together provides
guidance in critically ill patient management
and strong trending data for more meaningful
decision making (see Fig. 5.2). Reuter et al.
(2002) found that SVV predicted preload
changes and volume responsiveness in a study
of 20 mechanically ventilated postoperative
cardiac surgery patients. SVV is increasingly
used to assess fluid responsiveness whether
measured by arterial-based systems or by
Doppler technologies (see Fig. 5.3).
309
Figure 5.2 Mechanisms of SVV during positive
pressure ventilation.
Reprinted with permission from McGee (2009). A
simple physiologic algorithm for managing
hemodynamics using stroke volume and stroke
volume variation: Physiologic optimization
program. Journal of Intensive Care Medicine, 24,
352–366. © SAGE.
310
Figure 5.3 SVV and fluid responsiveness.
Reprinted with permission from McGee (2009). A
simple physiologic algorithm for managing
hemodynamics using stroke volume and stroke
volume variation: Physiologic optimization
program. Journal of Intensive Care Medicine, 24,
352–366. © SAGE.
311
Figure 5.4 Physiologic optimization program
using Stroke Volume Variation (SVV) and
Stroke Index (SI).
Reprinted with permission from McGee (2009). A
simple physiologic algorithm for managing
hemodynamics using stroke volume and stroke
volume variation: Physiologic optimization
program. Journal of Intensive Care Medicine, 24,
352–366. © SAGE.
Specific delivery systems for pulse contour
analysis and measurement of SVV follow.
FloTrac/Vigileo®
This method of hemodynamic analysis
incorporates a FloTrac transducer in an arterial
catheter system and a Vigileo monitor,
calculating CCO by analysis of pulse pressure
derived from arterial waveforms. Saraceni et al.
(2011) found underestimation of CO compared
with PAC thermodilution techniques but others
have found acceptable agreement between
FloTrac and PAC in cardiac surgery and
critically ill ventilated patients (Mayer et al.,
2009; Senn et al., 2009). The Vigileo monitor
also tracks central venous oxygenation in the
right atrium (RA) (ScvO2) using a special CVC,
based upon all venous admixture except that
supplied by the coronary venous system. This
allows for continuous ScvO2, CO, and SVV
displays.
312
Benes and colleagues (2010) found significantly
lower rates of postoperative complications and
lower lactate concentrations in high-risk
patients undergoing major abdominal surgery
managed with Vigileo/FloTrac monitoring
compared with controls. Liu et al. (2010)
compared the use of SVV and arterial-based
calculations of CO with traditional PAC values
in cardiac surgery patients, detecting strong
correlation between arterial CO measures and
CCO obtained from PACs. The experimental
group had fluid management targeted to SVV <
10%, using colloid boluses of 3 ml/kg. Patients
in the Vigileo-managed group had significantly
improved
outcomes
including
fewer
hypotensive epidodes, fewer complications, and
reductions in serum lactate. Continuous
trending to guide interventions allows for rapid
evaluation of patient changes and prevention of
deterioration (Marik et al., 2009). The
FloTrac®/Vigileo system may not be useful in
rapidly changing conditions, immediate
post-cardiopulmonary
bypass,
aortic
regurgitation, hepatic cirrhosis, or in patients
undergoing
intra-aortic
balloon
counterpulsation (Mayer et al., 2009).
Takala et al. (2011) reported on early
noninvasive
CO
monitoring
in
hemodynamically unstable medical-surgical
patients in three ICUs in Switzerland. Patients
were randomized to FloTrac arterial systems, or
to a control group (total n = 386).
313
Hemodynamic instability was identified by any
of the following criteria: clinically relevant
hypotension (<90 mmHg), evidence of cerebral
hypoperfusion, or acute drops in urinary output
following hypotension; clinical evidence of
hypovolemia; oliguria; elevated blood lactate;
or acute changes in mental status related to
hemodynamic state. Although the intent of the
study was that the experimental group would
stabilize more rapidly, findings revealed no
differences in patients reaching hemodynamic
stability within 6 h and enrolled patients
showed similar patterns of ICU and hospital
length of stays. Research on outcomes is
ongoing and definitive evidence on patient
outcomes remains inconclusive, though
promising, in targeted patient conditions.
Transpulmonary dilution techniques
The transpulmonary thermal-dye dilution
techniques assess ventricular preload by
estimation of intrathoracic blood volume
(ITBV), global end-diastolic volume (GEDV),
and extravascular lung water (EVLW).
Measurements may be by temperature (e.g.,
PiCCO®, PULSION Medical Systems, Munich,
Germany) or by lithium (e.g., LidCO® LidCO
Group PLC, London, UK). These systems
measure normovolemia and hypovolemia in a
range of clinical applications (Benington,
Ferris, and Nirmalan, 2009). They also
estimate CCO and the major limitation involves
314
changes induced by altered vascular compliance
(Vincent et al., 2011). EVLW has been shown to
estimate pulmonary edema and values higher
than 10 ml/kg are consistent with ARDS
(Benington, Ferris, and Nirmalan, 2009). The
pulse contour cardiac output (PiCCO) system
continuously calculates and displays SVI and
SVV, allowing for interventional assessment on
these
indicators.
In
a
multisite
noninterventional study, patient management
and outcomes using PiCCO were compared to
PAC use in over 300 critically ill patients from
eight ICUs in four countries (Uchino et al.,
2006). While selection of monitoring systems
was not controlled in this study, outcomes were
compared and patients with PiCCO systems had
fewer ventilator-free days and a higher positive
fluid balance. Final multivariate analysis did
not show significant differences between types
of monitoring device and the authors primarily
demonstrated that PACs were used more often
in patients requiring inotropes and PiCCO was
selected more often for patients exhibiting
vasodilatory
shock.
While
helpful
in
demonstrating the need for further controlled
trials, conclusions remain elusive for patient
outcomes in this study (Uchino et al., 2006).
Berkenstadt et al. (2001) studied the
effectiveness of the PiCCO system in 15
neurologic surgery patients undergoing brain
tumor resection or aneurysm repair and
reported successful SVV responsiveness
315
detection to guide fluid management. The
greatest drawback of the use of PiCCO is the
requirement for repeated calibrations for
accuracy. Research continues and published
guidelines are not yet available to guide
practitioners in the selection of patient
conditions and treatment protocols for
management of these systems.
Passive leg raising
Elevation of lower extremities results in a
natural fluid bolus through venous return,
potentially predicting responsiveness to a fluid
bolus naturally. This technique involves
elevating both lower extremities 45° for 4–5
min. Monnet et al. (2006) found that critically
ill patients responded favorably to passive leg
raising (PLR) techniques. In a study of 35
patients with circulatory failure, Jabot et al.
(2009) identified stronger patient response to
PLR when the patient moved from
semirecumbant positions to supine with
simultaneous leg raising rather than simple
elevation of legs from the supine position. PLR
was associated with significant changes in
hemodynamic measurements assessed by the
PiCCO system. This technique assesses fluid
responsiveness in patients regardless of
respiratory status or cardiac arrhythmias and is
considered to estimate the result of a 300–500
ml fluid challenge. In a meta-analysis of nine
studies, Cavallaro et al. (2010) verified the
316
found correlation between improved CO
following PLR and its ability to assess patient
fluid responsiveness despite respiratory status
or arrhythmias. Teboul and Monnet (2008)
identified PLR as the only reliable method for
assessing
volume
responsiveness
in
spontaneously
breathing
patients
but
recommended further study.
SVV protocols for management
McGee (2009) suggests that SVV greater than
13% indicates volume responsiveness and
recommends that 1 liter of normal saline be
administered over 10–15 min. Colloids or
reductions in crystalloid may be clinically
indicated based on the patient (McGee, 2009)
and results of fluid challenges should be
continuously monitored by stroke index or CO
variables. The use of an algorithm for
optimization of fluid based on stroke index is
promoted (McGee, 2009). See Figure 5.4
In summary, protocols are emerging for
monitoring patients with threats to tissue
oxygen delivery. Many studies described in this
chapter enrolled small numbers of patients and
lack generalizability. The need for more
controlled trials in this area is paramount to
guide practice by identifying patient parameters
in which optimization affects patient outcomes
in a more predictable manner for critically ill
adults admitted with complex pathologies. As
recommended by Garcia and Pinsky (2011),
317
collective
measures
of
fluid
status,
responsiveness, and tissue oxygenation must be
analyzed with clearly defined data assessing
circulatory adequacy such as lactate or anion
gap measurements to better define successful
treatment end points. This goal continues.
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326
Chapter 6
Monitoring for neurologic
dysfunction
Janice L. Hinkle1 and Carey Heck2
1
Washington, DC, USA
2
Jefferson School of Nursing, Philadelphia,
PA., USA
Physiological guidelines
Neurologic dysfunction can result from a
variety of pathophysiologic changes. Causes
include neurologic (head injury, stroke, brain
tumors, encephalopathy, etc.), toxicological
(drug overdose, alcohol intoxication, etc.), or
metabolic (hepatic or renal failure, diabetic
ketoacidosis, etc.) disruption. The wide variety
of clinical problems that can lead to neurologic
dysfunction in adult patients is part of what
makes nursing surveillance in this population
such a challenge.
Intact anatomic structures of the brain and
spinal cord are needed for normal neurologic
function. The two hemispheres of the cerebrum
must communicate, via an intact corpus
callosum, and the lobes of the brain (frontal,
parietal, temporal, and occipital) must
327
communicate and coordinate their specific
functions. Other important brain structures
include the cerebellum and the brain stem. The
cerebellum has both excitatory and inhibitory
actions and is largely responsible for
coordination of movement. The brain stem
contents are essential for brain and body
functions with areas that control heart rate,
respirations, and blood pressure (Smeltzer et
al., 2010).
The spinal cord is a long cylindrical structure
that begins in the medulla and ends at the
lumbar vertebrae L1–L2 (Bader and Littlejohns,
2004, 2010). It is the “main highway” for
ascending and descending fiber tracts that
connect the brain to the spinal nerves and is
responsible for reflexes. Disruptions in the
anatomic structures of the brain and spinal
cord can result from trauma, edema, pressure
from tumors, or other mechanisms, such as an
increase or decrease in the circulation of blood
or cerebrospinal fluid (CSF).
Increased intracranial pressure
The rigid cranial vault contains brain tissue
(1400 g), blood (75 ml), and CSF (75 ml)
(Smeltzer et al., 2010). The volume and
pressure of these three components are usually
in a state of equilibrium and produce a normal
ICP.
328
The Monro–Kellie hypothesis states that,
because of the limited space for expansion
within the skull (a closed box), an increase in
any one of the components causes a change in
the volume of the others (Bader, 2006a; Bader
and Littlejohns, 2004, 2010). Because brain
tissue has limited space to expand,
compensation typically is accomplished by
displacing or shifting CSF, increasing the
absorption or diminishing the production of
CSF, or decreasing cerebral blood volume.
Without compensatory changes, ICP begins to
rise. Under normal circumstances, minor
changes in blood volume and CSF volume occur
constantly as a result of alterations in
intrathoracic pressure (coughing, sneezing,
straining), posture, blood pressure, systemic
oxygen and carbon dioxide levels (Hickey,
2009).
Increased intracranial pressure (ICP) occurs in
many patients with acute neurologic conditions
because pathologic conditions alter the
relationship between intracranial volume and
ICP. Although elevated ICP is most commonly
associated with head injury, it may also be seen
as a secondary effect in other conditions, such
as brain tumors, subarachnoid hemorrhage, as
well as toxic and viral encephalopathies
(Smeltzer et al., 2010). Increased ICP from any
cause decreases cerebral perfusion, stimulates
further swelling (edema), and may shift brain
329
tissue, resulting in herniation, a dire and
frequently fatal event (Smeltzer et al., 2010).
Decreased cerebral blood flow
Increased ICP may reduce cerebral blood flow
(CBF) or decrease cerebral perfusion and this
can result in ischemia and cell death (Patho
puzzler, 2007). In the early stages of cerebral
ischemia, the vasomotor centers are stimulated
and the systemic pressure rises to maintain
CBF. Usually, this is accompanied by a slow
bounding pulse and respiratory irregularities.
These changes in blood pressure, pulse, and
respiration are important clinically because
they suggest increased ICP (Smeltzer et al.,
2010).
The concentration of carbon dioxide in the
blood and in the brain tissue also plays an
important role in the regulation of CBF. An
increase in the arterial partial pressure of
carbon dioxide (PaCO2) causes cerebral
vasodilation, leading to increased CBF and
increased ICP. A decrease in PaCO2 has a
vasoconstrictive effect, limiting blood flow to
the brain. Decreased venous outflow may also
increase cerebral blood volume, thus raising
ICP (Smeltzer et al., 2010).
Cerebral edema or swelling is defined as an
abnormal accumulation of water or fluid in the
intracellular space, extracellular space, or both,
associated with an increase in the volume of
330
brain tissue. Edema can occur in the gray,
white, or interstitial matter. As brain tissue
swells within the rigid skull, several
mechanisms attempt to compensate for the
increasing
ICP.
These
compensatory
mechanisms include autoregulation as well as
decreased production and flow of CSF.
Autoregulation (see Fig. 6.1) refers to the
brain’s ability to change the diameter of its
blood vessels to maintain a constant CBF
during alterations in systemic blood pressure.
This complex mechanism can be impaired in
patients who are experiencing a pathologic and
sustained increase in ICP (Smeltzer et al.,
2010).
331
Figure 6.1 Cerebral autoregulation. The Major
physiological system involved in the complex
regulation of blood pressure. Dotted lines
represent local autoregulation, solid lines
represents neural influences, and dashed lines
represents neuroendocrine influence. SNS,
sympathetic nervous system.
Adapted from figure 1.2 Cerebral autoregulation
and
blood
flow
at
available
www.electrical-res.com.
Cerebral response to increased
intracranial pressure
As ICP rises, compensatory mechanisms in the
brain work to maintain blood flow and prevent
secondary neurologic damage. The brain can
maintain a steady perfusion pressure if the
arterial systolic blood pressure is 50–150
mmHg and the ICP is less than 40 mmHg.
Changes in ICP are closely linked with cerebral
perfusion pressure (CPP). The CPP is calculated
by subtracting the ICP from the mean arterial
pressure (MAP). For example, if the MAP is 100
mmHg and the ICP is 15 mmHg, then the CPP
is 85 mmHg. The normal CPP is 70–100 mmHg
(Hickey, 2009). As ICP rises and the
autoregulatory mechanism of the brain is
overwhelmed, the CPP can increase to greater
than 100 mmHg or decrease to less than 50
mmHg. Patients with a CPP of less than 50
mmHg experience irreversible neurologic
damage. Therefore, the CPP must be
332
maintained and monitored to ensure adequate
blood flow to the brain. If ICP is equal to MAP,
cerebral circulation ceases (Smeltzer et al.,
2010).
A clinical phenomenon known as Cushing’s
response (or Cushing’s reflex) is seen when CBF
decreases significantly (Patho puzzler, 2007).
When ischemic, the vasomotor center triggers
an increase in arterial pressure in an effort to
overcome the increased ICP. A sympathetically
mediated response causes an increase in the
systolic blood pressure with a widening of the
pulse pressure and cardiac slowing. This
response is seen clinically as an increase in
systolic blood pressure, irregular respirations,
and reflex slowing of the heart rate
(bradycardia) (Andrews, 2011). It is a late sign
requiring immediate intervention but perfusion
may be recoverable if Cushing’s response is
treated rapidly (Smeltzer et al., 2010; Wyatt,
Moreda, and Olson, 2009).
At a certain point, the brain’s ability to
autoregulate
becomes
ineffective
and
decompensation (ischemia and infarction)
begins. When this occurs, the patient exhibits
significant changes in mental status and vital
signs. The bradycardia, hypertension, and
bradypnea associated with this deterioration
are known as Cushing’s triad, a grave sign
(Smeltzer et al., 2010). At this point, herniation
of the brain stem and occlusion of the CBF
333
occur if therapeutic intervention is not initiated.
Herniation refers to the shifting of brain tissue
from an area of high pressure to an area of
lower pressure. The herniated tissue exerts
pressure on the brain area into which it has
shifted, which interferes with the blood supply
in that area. Cessation of CBF results in
cerebral ischemia, infarction, and brain death.
While the following sections address various
aspects of neurological monitoring individually,
the advanced practice nurse needs to keep in
mind
that
currently
multimodal
neuromonitoring is commonly used to guide
therapy (Cecil et al., 2011).
Rapid assessment of neurologic
dysfunction in intensive care unit
patients
Monitoring elements
It is vital for advanced practice nurses to
identify the signs and symptoms of increased
ICP early while treatments can still be effective.
The first and perhaps most important early sign
critical to nursing surveillance is decrease in the
level of consciousness (LOC). The LOC is most
often monitored with the Glasgow Coma Scale
(GCS) (see Fig. 6.2).
334
Figure 6.2
application.
Glasgow
Coma
Scale
and
From Hickey (2009). © LWW.
Pupillary dysfunction (most often one larger
and slower to react pupil), changes in vision
and
extraocular
movements
(EOMs),
deteriorating motor function, headache, and/or
335
vomiting (Wyatt, Moreda, and Olson, 2009) are
additional signs of decreasing LOC. Changes in
the vital signs, especially those associated with
blood pressure, are considered a late sign
reflecting pressure on the brain stem (Wyatt,
Moreda, and Olson, 2009).
Evidence-based treatment guidelines
Advanced practice nurses often begin care in
the Emergency Department (ED) and there are
published guidelines for nursing surveillance of
the neurological system of the patient in the ED
who has evidence of cerebral contusion,
subdural, epidural, subarachnoid hemorrhage,
or other intracranial injury identified on
computed tomography (CT) scan. These
guidelines state that neurological checks must
be performed and documented on a
neurological
flow
sheet
(Neurological
Monitoring Guideline, 2010). Monitoring of the
GCS, pupils, and grips/grasps should occur
every 15 min for the first hour and then every
30 min for the next 6 h and hourly there after
(Neurological Monitoring Guideline, 2010).
Best practice guidelines for nursing surveillance
of the neurological system of patients with head
injuries and other intracranial injury once they
reach the ICU include serial GCS (recognizing
the limitations of this technique) plus inclusion
of other neurological data (Rauen et al., 2008).
Other recommended data include assessment of
brain stem reflexes, eye examination (pupil
336
reactions and EOMs), vital signs (respiration
depth, rate, and pattern). Best practices also
include consideration of clinical state,
concurrent injury, and drug use (Rauen et al.,
2008).
Best practices for the rapid assessment of
neurologic dysfunction in patients who have
had an acute ischemic stroke recommend the
use of the National Institute of Health Stroke
Scale (NIHSS) (see Fig. 6.3) (Gocan and Fisher,
2008; Summers et al., 2009). A complete
NIHSS is recommended upon admission to the
ICU and an abridged version can be performed
when more frequent assessment is needed
(Summers et al., 2009).
337
Figure 6.3 National Institute of Health Stroke
Scale (NIHSS).
338
Clinical Pearls—Patient
Management and Treatment
Some advanced practice nurses responsible
for the orientation and ongoing education of
staff in neurological intensive care units
(ICUs) use laminated “BRAIN cards”
(Presciutti and Finck, 2011). BRAIN stands
for Brain Resuscitation: Advanced Indicators
in Neuromonitoring. The cards are a
reference for registered nurses at the bedside
to quickly access information that may help
novice nurses become familiar with therapies
and parameters. Experienced nurses may use
it as a teaching tool. Figure 6.4 contains the
basic resuscitation as well as the basic and
advanced neuromonitoring parameters that
appear on the card.
339
Figure 6.4 Two sections of BRAIN card.
A relatively new device, the pupillometer, is
being used for nursing surveillance of pupil
reactions (Bader, 2006a; Cecil et al., 2011). A
pupillometer is a handheld battery-operated
device about the size of a mobile phone. A
microprocessor-based optical scanner
captures and analyzes pupil dynamics. The
device displays the maximum and minimum
aperture of the pupil before and after a light
stimulus, the percentage change in the pupil,
and several velocities (Bader, 2006a).
Preliminary research indicates that the
pupillometer is an easy and rapid adjunct to
assess neurological changes of the pupils in
340
patients with traumatic brain injury (TBI)
(Cecil et al., 2011) but insufficient evidence
exists to warrant the widespread application
of this device.
Some recommend the rapid assessment of
neurological dysfunction compromised by
depressed LOC or concurrent drug therapy
be supplemented. Neuroimaging and
neurophysiological evaluation
(electroencephalographic) are the
recommended forms of supplemental
monitoring (Rauen et al., 2008).
Intracranial pressure monitoring
Monitoring elements
Nursing surveillance of ICP can be
accomplished using a variety of devices
including a ventriculostomy, a parenchymal
catheter, a subarachnoid screw or bolt, a
subdural device, an epidural device, or a hybrid
or combination of these that are placed inside
the cranial vault (Bader, 2006a). Table 6.1
provides an overview of the advantages and
disadvantages of ICP devices (Bader and
Littlejohns, 2004, p. 201). These devices make
use of a variety of technologies to measure the
pressure including pneumatic transducers,
microchip transducers, fiber-optic technology,
341
or an air pouch (Bader and Littlejohns, 2004).
Some consider “normal” ICP to be 0–10 mmHg
(Moreda, Wyatt, and Olson, 2009) with 15
mmHg as the upper limit of normal (Hickey,
2009); other authors state 10–20 mmHg is
“normal” (Patho puzzler, 2007).
Table 6.1 Intracranial pressure monitoring
options.
From Bader and Littlejohns (2004). © Elsevier.
Monitoring
Device
Transducer Advantages
Type
Disadvantage
Ventriculostomy ESG
ISG
F
Gold standard Most difficult t
Allows CSF
insert—small
drainage
ventricle or
ventricular shif
Good waveform
May occlude
F—may
malfunction
ISG and
F—unable to
rezero
Parenchymal
Quick
insertion
Low
complication
rate
ISG
F
342
Good waveform
F—catheter
breakage
ISG—catheter
displacement
ISG and
F—unable to
rezero
Subarachnoid
screw
ESG
F
Quick
insertion
Epidural
ESG
F
Extradural
Indirect
Easy insertion measure
Poor waveform
Poor accuracy
Subdural
ESG
ISG
F
Tunnel system
May be
inserted
postoperatively
through
craniotomy
From March K: Intracranial pressure
monitoring
and
assessing
intracranial
compliance in brain injury, Crit Care Nurs Clin
North Am 12(4):429–36, 2000.
CSF, Internal strain gange; ESG, external strain
gauge; F, fiberoptic; ISG, internal strain gauge.
Bader, M. K., & Littlejohns, L. R. (Eds.)· (2004).
AANN core curriculum for neuroscience
nursing (4th ed.). St. Louis: Elsevier. used with
permission
Evidence-based treatment guidelines
The Neuro-Intensive Care and Emergency
Medicine (NICEM) section of the European
343
Fair waveform
Occlusion of
device—debris
in device (brain
dura, clot)CSF
leak
Poor waveform
Poor accuracy
May be
compressed as
brain swells
Society of Intensive Care Medicine states that
there are insufficient data to recommend ICP
monitoring and management as a standard of
care in all brain-injured patients (Andrews et
al., 2008). However, the evidence is “good
enough” to recommend ICP monitoring in all
potentially salvageable patients with a severe
TBI (defined as GCS ≤ 8) with abnormal
findings on CT scan (Andrews et al., 2008).
Other summaries support ICP monitoring in
severe TBI (Littlejohns and Bader, 2009). There
are much lower levels of evidence for ICP
monitoring in patients with intracranial
hemorrhage,
subarachnoid
hemorrhage,
hydrocephalus, sylvian arachnoid cysts,
cerebral fat embolism, fulminant hepatic
failure, acute ischemic stroke, or meningitis
(Littlejohns and Bader, 2009).
Several authors mention the ventriculostomy as
the “gold standard” or the most accurate for ICP
monitoring (Andrews et al., 2008; Bader and
Littlejohns, 2004; Brain Trauma Foundation,
2007; Littlejohns and Bader, 2009). The
NICEM consensus stated that “in general, ICP
and CPP target values should be ≤20 mmHg
and ≥50–70 mmHg respectively” (Andrews et
al., 2008, p. 1365) and others concurred (Brain
Trauma Foundation, 2007; Littlejohns and
Bader, 2009). Others suggest ICP should be
≤20–25 mmHg (Bader, 2006a; Blissitt, 2006;
Cecil et al., 2011) and CPP 60–70 mmHg
344
(Blissitt, 2006). Clear guidelines remain elusive
and further research is needed.
Clinical Pearls—Patient
Management and Treatment
A common concern of ICU nurses caring for
patients with ICP monitoring is how nursing
interventions affect ICP. The ICP reference
range should be determined for each patient
taking into consideration the physician’s
orders, the underlying pathology, and the
plan of care (Bell, 2009). The nurse should
monitor pulmonary hygiene and the effects of
interventions, such as suctioning and patient
positioning on ICP (Bell, 2009). Current
research shows that the routine chest
percussion therapy (using specialty beds) is
safe to perform in patients with monitoring
in place (Olson et al., 2009a, 2010). One
study reported that a small number of
patients had ICP values greater than 20
mmHg but there was no trend toward overall
worsening of ICP immediately after oral care
(Prendergast et al., 2009). Regular oral care
is known to decrease the incidence of
ventilator-assisted pneumonia but larger
well-designed studies are needed to fully
understand ICP and oral care. It is
recommended that nursing care be planned
345
at intervals to allow patients with elevated
ICP to stabilize (Bell, 2009).
Elevating the head-of-bed (HOB) should be
based on the underlying disease process of
the patient to help control ICP (Bell, 2009).
Much research has gone into HOB elevation
and ICP but still there are not high levels of
evidence to support practices (Littlejohns
and Bader, 2009). Patients who have had a
stroke are thought to benefit from horizontal
backrest positions to optimize CPP
(Littlejohns and Bader, 2009). Maintaining
the HOB at 30° reduces ICP and improves
CPP without concomitant decrease in
cerebral oxygenation in patients who have
had a TBI (Littlejohns and Bader, 2009). In
patients with other neurological injuries, ICP
is improved with HOB at 30° but the CPP is
not improved (Littlejohns and Bader, 2009).
As mentioned in the section on rapid
neurological assessment, the monitoring of
pupils is being conducted in some
institutions with a new device, the
pupillometer. Preliminary research indicates
that the monitoring of constriction velocities
and pupil reactivity aids in the detection of
increased ICP (Cecil et al., 2011).
There is also preliminary research on the
analysis of ICP waveforms to measure
346
cerebral compliance (Fan, 2006; Fan et al.,
2008; Hickey, Olson, and Turner, 2009).
With additional research these techniques
may prove useful as a clinical tool to measure
compliance and detect early deterioration in
those with neurological injury.
Measuring brain temperature
Fever (temperature ≥38.3 °C) is known to
exacerbate secondary neuronal damage in all
forms of brain injury and has been shown to
adversely affect neurologic outcomes (Badjatia,
2009). A more aggressive approach to actively
controlling patient temperature is supported by
studies that appear to show improved outcomes
when normothermia is maintained (Polderman
and Herold, 2009). Brain temperatures exceed
core body temperatures (Bader and Littlejohns,
2010, p. 192) and so there may be a benefit to
monitoring brain temperatures in addition to
core temperatures (see Table 6.2). Monitoring
brain temperature using an invasive device,
such as a thermistor, may detect episodes of
neural hyperthermia, which, if untreated, could
lead to further neurological injury (Mcilvoy,
2007). One literature review suggested that
brain temperature is higher than core
temperature and without monitoring brain
temperature, detection of fever and its effects
may be limited (Mcilvoy, 2007). Monitoring
347
brain temperature may provide the clinician
with additional information that has the
potential to improve patient outcomes.
Table 6.2 Differences in brain and body
temperatures.
Adapted from Bader and Littlejohns (2010). ©
American Association of Neuroscience Nursing.
Brain temperature 0.5–1 °C higher than core
and jugular
Brain temperature 0.3–1.9 °C higher than
bladder
Brain temperature 0.1–2 °C higher than rectal
Deep white matter 0.5–1 °C higher than
cortical
There are greater differences with
temperatures higher than 38 °C
Evidence-based treatment guidelines
No evidence-based treatment guidelines to
support the use of the routine measurement of
brain temperature were identified.
Clinical Pearls—Patient
Management and Treatment
Brain temperature monitoring is relatively
easy as it is included in several multimodality
348
systems. Some suggest preventing brain
hyperthermia (>38.5 °C) with cooling
interventions following TBI (Cecil et al.,
2011).
Brain tissue O2 monitoring
Monitoring elements
Two methods exist to measure brain tissue
oxygenation: jugular venous saturation (SjO2)
and partial pressure brain tissue oxygen
(PbtO2). The former measures the oxygen
saturation of hemoglobin as it exits the cerebral
circulation via a catheter in the internal jugular
vein and provides a means of identifying global
cerebral oxygenation (Bader, 2006b). Normal
findings for SjO2 are 55–75% saturation (Bader
and Littlejohns, 2004; Wiegand and American
Association of Critical Care Nurses [AACN],
2011). The latter method monitors the balance
between cerebral oxygen delivery and oxygen
consumption and is obtained by the placement
of a catheter within the brain parenchyma. This
method has the ability to detect regional
cerebral oxygenation (Andrews et al., 2008;
Bader and Littlejohns, 2004). Normal values
for PbtO2 are between 25 and 35 mmHg (Bader
and Littlejohns, 2004).
349
Evidence-based treatment guidelines
There are limited clinical studies supporting the
use of cerebral tissue oxygenation monitoring
(Littlejohns and Bader, 2009). However,
several authors recommend initiating treatment
for SjO2 < 50% and PbtO2 < 20 mmHg (Bader,
2006b; Bader and Littlejohns, 2004; Brain
Trauma Foundation, 2007).
Clinical Pearls—Patient
Management and Treatment
Changes seen in oxygen delivery and
consumption in the brain may occur before
clinical signs are seen in the patient. Careful
and diligent monitoring of changes and
trends will provide the nurse with
information that can be used to guide
treatment and prevent hypoxia and
subsequent cerebral ischemia. SjO2 < 40%
represents global cerebral ischemia and has
been associated with poor outcomes
(Wiegand and AACN, 2011). Cerebral tissue
hypoxia is seen in PbO2 < 15 mmHg with
cerebral tissue death occurring at 5 mmHg
(Bader and Littlejohns, 2004; Wiegand and
AACN, 2011).
350
Microdialysis
Monitoring elements
Microdialysis allows for the continuous
measurement of tissue chemistry across a
semipermeable membrane in the extracellular
space of the brain (Andrews et al., 2008; Bader
and Littlejohns, 2004, 2010). Biochemical
markers including the lactate/pyruvate ratio,
glucose, and glutamate levels are monitored.
Changes in these biomarkers are early
indicators of cerebral hypoxia and ischemia
(Andrews et al., 2008; Bader and Littlejohns,
2004, 2010).
Evidence-based treatment guidelines
No evidence-based treatment guidelines were
identified to support the routine use of cerebral
microdialysis. However, several authors have
recommended the use of microdialysis in
patients with TBI who require intracranial
monitoring (Bellander et al., 2004; Cecil et al.,
2011).
Clinical Pearls—Patient
Management and Treatment
There is currently a lack of consensus
regarding treatment parameters and
351
indications for use of cerebral microdialysis
(Bader and Littlejohns, 2004, 2010). This
monitoring modality has been studied in
neurological patients with TBI (Cecil et al.,
2011), subarachnoid hemorrhage (SAH),
epilepsy, and stroke (Bader, 2006a). When
considering adding microdialysis to the
nursing surveillance, the individual patient’s
clinical course, the overall treatment goals,
outcomes, and risk/benefit status must be
considered.
Electrophysiological monitoring
Monitoring elements
Electroencephalography (EEG) is a technology
used to measure cerebral electrical activity as
an electrochemical phenomenon and reflects
the metabolic and physiological state of
cerebral tissue (Bader and Littlejohns, 2010).
The placement of multiple surface electrodes
detects electrical impulses that generate a
waveform reflecting chemical events at the
tissue and cellular levels (Bader and Littlejohns,
2010).
Evidence-based treatment guidelines
Surprisingly there are very few evidence-based
guidelines
for
EEG
monitoring.
The
352
evidence-based guidelines for the management
of spontaneous intracerebral hemorrhage (ICH)
state that “continuous EEG monitoring is
probably indicated in ICH patients with
depressed mental status that is out of
proportion to the degree of brain injury”
(Morgenstern et al., 2010, p. 2116). Further, the
guidelines state that those patients with
seizures identified on EEG need to be treated
with antiepileptic drugs (Morgenstern et al.,
2010).
Clinical Pearls—Patient
Management and Treatment
There are a number of clinical indications for
nursing surveillance of the neurologic system
using EEG monitoring. It is used mainly for
the evaluation of unconscious patients to
detect subclinical seizure activity and to
monitor the onset and/or progression of
cerebral ischemia (Bader and Littlejohns,
2010). It is used to evaluate patients post
cardiac arrest as well as patients in coma
states including barbiturate coma (Bader and
Littlejohns, 2010). It is also used as a
cerebral evaluation of pharmacologically
paralyzed states. One study suggested that a
mathematical model of EEG recording might
be useful in differentiating between patients
in a vegetative state and those with a higher
353
LOC following severe brain injury (Boly et al.,
2011).
The BiSpectral index monitoring
Monitoring elements
BiSpectral ndex (BIS) monitoring was originally
developed for use during surgery as an adjunct
to sedation monitoring for general anesthesia
but has been shown to be a useful tool in
managing the sedation levels of the general
critical care patient. The BIS monitor is a
processed EEG-based parameter used to assess
individual LOC and sedation (Arbour et al.,
2009; Bader and Littlejohns, 2010). Through
the application of a sensor placed on the
individual’s forehead, information obtained is
calculated into a numeric value correlating with
the patient’s LOC. Many factors may affect BIS
readings so an understanding of the
significance of the parameters obtained is
crucial for data interpretation. Factors such as
analgesic
and
neuromuscular
blockade
administration, pain, muscle artifact, sleep
patterns, or altered neurologic states due to a
variety of pathologies have the potential to
increase or decrease this value (Fraser and
Riker, 2005; Sessler, Grap, and Ramsay, 2008).
354
Evidence-based treatment guidelines
Several studies evaluating sedation levels of
patients in the ICU have shown BIS monitoring
to be an effective adjunct tool in decreasing the
use of sedative medications without increasing
patient complications. However, research to
date does not support the use of BIS monitoring
alone for the management of sedation in the
critically ill patient (Arbour et al., 2009;
Weaver et al., 2007). No evidence-based
treatment guidelines were identified for BIS
monitoring.
Clinical Pearls—Patient
Management and Treatment
Clinical observation augmented by
technology, such as BIS monitoring, is
considered by some to have the potential to
improve patient care (Olson et al., 2009b).
Since many factors may influence BIS data,
the practitioner should keep in mind that
technology is part of an integrated evaluation
of the patient and does not serve as a
replacement for clinical evaluation (Fraser
and Riker, 2005). Use of BIS monitoring
should take into account the overall
treatment goals of the patient’s plan of care.
BIS values and corresponding levels of
sedation are summarized in Table 6.3.
355
Table 6.3 BIS values and corresponding
levels of sedation
Adapted from Bader and Littlejohns (2004). ©
Elsevier.
BIS Corresponding level of sedation
value
100
Awake state, patient able to respond
appropriately to verbal stimulation
80
Patient able to respond to loud
verbal or limited tactile stimulation
such as mild prodding or shaking
60
Low probability of explicit recall,
patient unresponsive to verbal
stimulation
40
Patient unresponsive to verbal
stimulation, less responsive to
physical stimulation
20
Minimal responsiveness
0
No responsiveness mediated by
brain function, spinal reflexes may
be present
356
Transcranial Doppler
ultrasonograpy
Monitoring elements
Transcranial Doppler (TCD) ultrasonograpy is a
valuable technique for the advanced practice
nurse to have in the nursing surveillance
arsenal as it provides an indirect measure of
CBF by measuring the CBF velocity and can be
carried out at the bedside of the patient
(Littlejohns and Bader, 2009). TCD measures
blood flow velocities in the major branches of
the circle of Willis through bone windows in an
intact skull (see Fig. 6.5) (Wiegand and AACN,
2011). This measure supports the assessment
and monitoring of vasospasm severity,
localization of intracranial stenoses or
occlusions, detection of cerebral emboli,
monitoring of hemodynamic changes with
impaired
intracranial
perfusion,
and
assessment of therapeutic interventions on
intracranial hemodynamics (Wiegand and
AACN, 2011, p. 849).
357
Figure 6.5 The image on the left shows 4
windows of transcranial Doppler insonation.
Clockwise these are orbital, temporal,
submandifular, and foraminal. The image on
the right shows the 3 aspects of the temporal
window: 1) middle; 2)posterior; and 3)anterior.
Adapted with permission from Wiegand, D.J.L.,
and the American Association of Critical-Care
Nurses (AACN) (2011).
Evidence-based treatment guidelines
No evidence-based treatment guidelines were
identified for TCD use. Evidence for the
procedure comes from case studies, expert
opinion, or professional organization standards
without clinical studies to support the
recommendations (Wiegand and AACN, 2011).
The evidence for the use of TCDs in patients
with fulminant hepatic failure is an active area
358
of research (Bindi et al., 2008; Kawakami,
Koda, and Murawaki, 2010).
Clinical Pearls—Patient
Management and Treatment
TCD studies are used to measure CBF
velocity at intermittent intervals that vary
from institution to institution. Accuracy is
dependent on knowledge of neuroanatomy
and physiology, the correct placement and
angle of the probe, and the technical
competency of the individual performing the
study (Littlejohns and Bader, 2009; Wiegand
and AACN, 2011).
While not evidence-based, a common use of
TCDs is for the detection and monitoring of
vasospasm in patients who have had an SAH.
One study assessed the role of TCD in
optimizing the treatment of vasospasm using
hypervolemia/hypertension/hemodilution
therapy (Darwish, Ahn, and Amiridze, 2008).
Another study used TCD to monitor the
effects of HOB elevation on vasospasm
following SAH (Blissitt et al., 2006). These
avenues of research need further study.
359
Shunts
Monitoring elements
Shunts are small tubes made of Silast that
divert CSF from the ventricles or subarachnoid
space within the brain into other body cavities
to treat hydocephalus. The insertion of shunts
is one of the most common procedures
performed in many neurosurgical centers
(Bader and Littlejohns, 2010). Types include
ventriculoperitoneal,
ventriculoatrial,
ventriculopleural, and lumbar peritoneal shunts
(Bader and Littlejohns, 2010).
Evidence-based treatment guidelines
No evidence-based treatment guidelines could
be located for routine postoperative monitoring
of a newly placed shunt or to determine
whether a shunt is malfunctioning or not.
Clinical Pearls—Patient
Management and Treatment
Frequent vital signs and neurological checks
are needed in patients who have had a newly
inserted shunt to assess for complications of
intracerebral or subdural hematoma,
meningitis, or peritonitis (Bader and
Littlejohns, 2010). The cranial and peritoneal
360
(or alternate catheter site) incision needs to
be assessed for signs and symptoms of
wound infection (Bader and Littlejohns,
2010).
Routine strategies for detecting shunt
malfunction include clinical neurological
assessment, neuropsychological testing, and
neuroimaging (Petrella et al., 2009). One
study reported that in vivo shunt testing
using a constant rate infusion of normal
saline was easy, safe, and clinically useful,
especially when shunt malfunction was
suspected but not certain (Petrella et al.,
2009).
Neuromuscular transmission
Monitoring elements
Neuromuscular transmission, or stimulation, is
used to assess evoked responses (Bader and
Littlejohns, 2010). The main types include the
supramaxial stimulation to assess a single
twitch, the “train-of-four,” which comprises
four stimuli over 2 s, the double-burst
stimulation, and the titanic stimulation (Bader
and Littlejohns, 2004, 2010). The primary
indication is to monitor the peripheral nervous
system.
361
Evidence-based treatment guidelines
No evidence-based treatment guidelines could
be located for neuromuscular stimulation.
Clinical Pearls—Patient
Management and Treatment
The interpretation of evoked responses (to
stimulation) requires specialized training and
must be interpreted within the context of
other clinical assessment findings.
Management of cervical
stabilization devices
Monitoring elements
Cervical instability can result from many causes
including trauma, degenerative changes,
infectious causes, or neoplastic disease.
Depending upon the cause of the cervical
instability, treatment varies. Options include
surgical or nonsurgical interventions. Decisions
for treatment are made based on several
considerations including patient presentation,
the underlying cervical pathology, mechanical
and technical considerations of treatment,
patient preference, and surgeon expertise and
experience
(American
Association
of
Neuroscience Nurses [AANN], 2007; Bader and
362
Littlejohns, 2010). Nonsurgical management
for cervical instability as a result of traumatic or
nontrauma pathologies may include application
of a hard cervical collar or halo brace. These
may be used as an alternative to surgery in the
case of some vertebral fractures or as an
adjunct to surgery when placed post-operatively
to facilitate bony healing (Bader and
Littlejohns, 2010; Sarro et al., 2010). Surgical
management for cervical instability will vary
greatly from patient to patient (see Fig. 6.6).
Extensive pathology may require a combined
anterior/posterior approach while other
presentations may require only one of these
approaches (AANN, 2007). The use of
instrumentation (e.g., plates, wires, cages, or
screws) to provide internal fixation and
stabilization promotes bony healing and may be
part of a surgical treatment plan (AANN, 2007).
Atlantoaxial instability (C1–C2 instability),
often the result of degenerative, infectious, or
neoplastic causes, is typically treated with
surgery and instrumentation (Nockels et al.,
2007).
363
Figure 6.6 Cervical spine stabilization from
AANA (2007). Cervical Spine Surgery. A Guide
to Preoperative Patient Care. Used with
permission from AANA.
Evidence-based treatment guidelines
Recommendations for the management of
cervical instability due to traumatic injuries are
made in Early Acute Management in Adults
with Spinal Cord Injury: A Clinical Practice
Guideline for Health-Care Providers authored
by the Consortium for Spinal Cord Medicine
(2008) and in the Advanced Trauma Life
Support guidelines (American College of
Surgeons Committee on Trauma, 2012). These
guidelines recommend initial immobilization of
the neck in a hard collar for all patients with a
suspected cervical spine injury until definitive
diagnosis is established. Several authors have
recommended early surgical intervention in
364
traumatic spinal cord injuries (SCIs) to improve
neurologic outcomes (Consortium for Spinal
Cord Medicine, 2008). Others conclude that the
current evidence does not allow decisions to be
drawn regarding the potential benefits or harms
of spinal fixation surgery in patients with
traumatic spinal cord injury (Bagnall et al.,
2009). Review of the literature concerning
surgery for cervical instability due to causes
other than trauma reveals numerous small
studies and case reports of interventions and so
evidence-based recommendations for practice
cannot be made at this time.
Literature
is
limited
concerning
evidenced-based management of halo devices
and reveals the need for standardization of care
regarding these devices (Sarro et al., 2010).
Inspection of pin sites for signs of infection,
loosening of pins, or halo ring movement are all
considered to be standard aspects of nursing
management of halo devices (AANN, 2007;
Sarro et al., 2010).
Clinical Pearls—Patient
Management and Treatment
Regardless of the cause of cervical instability,
the importance of serial examinations to
detect motor and/or sensory changes cannot
be stressed enough. A complete motor and
365
sensory exam must be performed after any
application, removal, or manipulation of
stabilization device (Bader and Littlejohns,
2010). Changes in a patient’s clinical exam
must be reported promptly to the physician
or advanced practice clinician.
There exists an increased potential for skin
breakdown due to orthotic devices.
Meticulous care and inspection of areas at
high risk for skin breakdown (i.e., occiput)
are of paramount importance in any patient
evaluation (AANN, 2007; Bader and
Littlejohns, 2010).
Induced coma and sedation protocols
Monitoring elements
Therapeutic interventions provided in the ICU
may result in anxiety, pain, and agitation in the
critically ill patient, which can increase ICP and
adversely affect outcomes. The use of analgesics
and sedatives to ameliorate these unintended
side effects of care are a common management
strategy for ICP control and are vital for the
comfort and safety of patients (Bader and
Littlejohns, 2010; Brain Trauma Foundation,
2007;
Rangel-Castillo,
Gopinath,
and
Robertson, 2008; Wunsch and Kress, 2009).
Inadequate or excessive sedation, however, has
been shown to lead to significant patient
366
complications and therefore must be avoided
(Sessler, Grap, and Ramsay, 2008; Sessler and
Pedram, 2009). The neurologically impaired
patient
requires
frequent
neurologic
assessment and the practitioner must take this
into consideration when choosing agents for
sedation. The use of sedation in all patients, but
particularly in the neurologic patient, should be
based on patient needs and the indications for
their use reassessed regularly (Wyatt, Moreda,
and Olson, 2009).
High-dose barbiturate coma has been used as a
management strategy for reducing ICP
refractory to maximal medical and/or surgical
intervention (Bader and Littlejohns, 2010;
Brain Trauma Foundation, 2007). The
mechanism of action is a reduction of cerebral
metabolic
demand
through
cerebral
vasoconstriction and blood flow, which results
in decreased ICP (Hickey, 2009; Wyatt,
Moreda, and Olson, 2009). Significant side
effects of barbiturate coma may occur including
cardiac depression, hypotension, hypothermia,
and
immunosuppression,
and
careful
monitoring for these complications must be
ongoing (Bader and Littlejohns, 2010; Tobias,
2008). Due to the loss of neurologic exam with
induction of barbiturate coma, several authors
recommend neurophysiologic monitoring to
evaluate burst suppression activity since the
physical exam is of limited value in detecting
changes (Brain Trauma Foundation, 2007;
367
Tobias, 2008; Rangel-Castillo, Gopinath, and
Robertson, 2008).
Evidence-based treatment guidelines
There are no evidenced-based protocols for the
management of sedation for neurologic
conditions. Selection of agents is guided by the
individual practitioner’s judgment based on the
patient’s condition and treatment goals (Brain
Trauma Foundation, 2007; Rangel-Castillo,
Gopinath, and Robertson, 2008). Some authors
have recommended the use of short-acting
agents, which allow brief interruptions of
sedation to evaluate neurologic status
(Rangel-Castillo, Gopinath, and Robertson,
2008). When utilized, attention must be paid to
potential undesirable side effects, such as
hypotension, that may contribute to secondary
injury (Brain Trauma Foundation, 2007;
Tobias, 2008). Although barbiturate coma
reduces ICP, it has not been shown to improve
outcomes and therefore recommendations for
use as a first-line treatment choice are not
indicated (Bader and Littlejohns, 2010; Roberts
and Syndenham, 2009).
368
Clinical Pearls—Patient
Management and Treatment
The use of sedation clearly has advantages in
this population, particularly when increased
ICP is a concern. Care must be taken to
manage the deleterious effects of agitation
and pain on ICP, yet at the same time
avoiding oversedation. Oversedation can
mask a deteriorating neurologic exam, which,
if not recognized and acted upon
appropriately, could result in unfavorable
patient outcomes.
Research-based neurologic
protocols
Many of the clinical guidelines mentioned in
this chapter are research-based and contain
recommendations for monitoring neurological
conditions such as TBI (Brain Trauma
Foundation, 2007) and SCI (AANN, 2007;
Consortium for Spinal Cord Medicine, 2008).
However, no specific research-based protocols
for neurological monitoring were located.
Neurologic injury and trauma induce multiple
changes that are difficult to control, thus
randomized control trials remain difficult to
design and complete. However, continued
369
research is under way on many of the
techniques discussed within this chapter.
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379
Chapter 7
Monitoring for renal
dysfunction
Dawn Cooper
Medical Intensive Care Unit, Yale New Haven
Hospital, New Haven, CT., USA
Renal dysfunction in critically ill patients may
lead to catastrophic consequences. The
incidence of acute kidney injury (AKI) occurs in
over 20% of critically ill patients (Thakar et al.,
2009). The mortality rate of patients with AKI
in the critical care unit is 59%, with another 8%
who die before leaving the hospital (Uchino et
al., 2005). Unlike community-acquired AKI,
AKI in critically ill patients is most often
associated with more than a single insult
(Dennen, Douglas, and Anderson, 2010). The
most common causes of AKI in the critical care
unit are sepsis, followed by major surgery, low
cardiac output, hypovolemia, and medications.
Other causes of AKI are hepatorenal syndrome,
trauma, cardiopulmonary bypass, abdominal
compartment syndrome, rhabdomyolysis, and
obstruction (Uchino et al., 2005). AKI
negatively impacts clinical outcomes, prolongs
hospitalization, and can eventually lead to the
need for dialysis. The advanced practice nurse
380
plays a pivotal role in prevention, early
recognition, and prompt intervention of renal
dysfunction to optimize patient outcomes.
Acute kidney injury
The term acute kidney injury (AKI) is used to
describe several clinical conditions causing
acute kidney dysfunction. Prior to 2004, the
term “acute renal failure” was used to describe
acute kidney impairment. Acute renal failure
was a broad term that never had a standardized
definition, diagnosis criteria, or disease
stratification. The Acute Dialysis Quality
Initiative (ADQI) group began the formal work
of developing a consensus definition of acute
renal failure that eventually led to a definition
of AKI. The risk, injury failure, loss, and
end-stage renal disease (RIFLE) criteria
stratified the phases of AKI (Bellomo et al.,
2004). The RIFLE criteria are based on two
categories: creatinine and urinary output (see
Fig. 7.1).
381
Figure 7.1 RIFLE classification/staging system
for AKI.
Used with permission by Mehta et al. (2007). ©
BioMed Central.
*GFR: Glomerular Filtration Rate.
** ARF: Acute Renal Failure.
SCreat: Serum Creatinine, UO: Urinary output.
A patient can fulfill the criteria though a change
of one or both criteria in each category. The
patient is classified by the criterion that falls in
the most severe category. The Acute Kidney
Injury Network (AKIN) later developed the
definition of AKI as “a common clinical
problem defined by an abrupt (within 48 h)
increase in serum creatinine, resulting from an
382
injury or insult that causes a functional or
structural change in the kidney” (Molitoris et
al., 2007 p. 439). They later developed a staging
system of AKI. Table 7.1 identifies the stages of
AKI (Bellomo et al., 2004). The spectrum of
AKI ranges from the most subtle changes in
renal function to the most severe.
Table 7.1 AKIN Classification/Staging System
for Acute Kidney Injury.
Used with permission by Mehta et al. (2007). ©
BioMedCentral.
Stage Serum creatinine
criteria
Urine
output
criteria
1
Increase in serum
creatinine ≥0.3 mg/dl
(>26.4 µmol/l) or increase
to ≥150% to 200% to 300%
(>1.5–2 times) from
baseline
Less than
0.5 ml/
kg/h for
more
than 6 h
2*
Increase in serum
Less than
creatinine to >200–300% 0.5 ml/
(>2–3 times) from baseline kg/h for
more
than 12 h
3†
Increase in serum
creatinine to >300% (>3
times) from baseline (or
serum creatinine ≥4.0 mg/
dl (>354 µmol/l)
383
Less than
0.3 ml/
kg/h to
24 h to
Stage Serum creatinine
criteria
Urine
output
criteria
anuria for
12 h
*200–300% increase = two- to threefold
increase.
†Given wide variation in indications and timing
of initiation of renal replacement therapy
(RRT), individuals who receive RRT are
considered to have met the criteria for stage 3
irrespective of the stage they are in at the time
of RRT.
The Kidney Disease: Improving Global
Outcomes (KDIGO) workgroup recognized that
variablity in the recognition and treatment of
AKI continued despite the validation of the
RIFLE and AKIN (Acute Kidney Injury Work
Group, 2012). This group also developed a
staged approach to classifying AKI since it has
been widely identified that the risk for death
and the need for renal replacement therapy
increase as kidney disease progresses. The
classification and prevention areas of these
guidelines are more widely accepted, but
treatment for AKI and recommendations for
renal replacement are controversial because of
minimal supporting evidence (James et al.,
2013; Palevsky et al., 2013).
384
AKI is classified in one of three stages based on
severity. Staging is based on criteria that will
give the patient the highest stage. These three
stages are defined based on serum creatinine
levels and urinary output. For stage 1, serum
creatinine rises to 1.5–1.9 times baseline or
urinary output of <0.5 ml/kg/h for 6–12 h;
stage 2 is characterized by rising creatinine
2.0–2.9 times baseline or urinary output of
<0.5 ml/kg/h for ≥12 h; and stage 3 is
identified as 3.0 times baseline creatinine or
urinary output of <3.0 ml/kg/h for ≥24 h or
anuria for ≥12 h (KDIGO, 2012).
The need for renal replacement and risk of
death increase with increased stage. Despite the
method used to classify and stage AKI, early
recognition of renal impairment is essential to
prevent long-term renal impairment and
prevent complications. To date, there is no
classification or staging system of AKI that has
been proven to identify all patients with AKI.
Clinical judgment also plays a dominent role in
identifying patients at risk or with AKI.
Physiological guidelines
AKI is attributed to prerenal, intrarenal, or
postrenal pathology. Regardless of the etiology,
there are complex interactions between
vascular, tubular, and inflammatory factors.
The outcome is vasoconstriction, endothelial
injury, and activation of an inflammatory
385
response (Bagshaw et al., 2010). Identifying the
cause is critical to prevent or minimize renal
injury.
Prerenal injury
Prerenal injury is a consequence of renal
hypoperfusion from factors outside of the
kidney (Table 7.2). Under normal conditions,
about 20–25% of cardiac output, or 1100 ml/
min is received by the kidneys (Hall, 2011).
Autoregulatory mechanisms keep blood flow
and pressure constant to maintain adequate
renal tissue oxygenation. The autoregulatory
properties of the kidney can tolerate a large
reduction in perfusion before ischemic changes
occur (Hall, 2011). The autoregulatory response
can be negatively affected by many conditions
that include atherosclerosis, hypertension,
advanced age, and the presence of chronic
kidney disease (Longo et al., 2012).
Medications, such as angiotension-converting
enzyme (ACE) inhibitors and angiotension
receptor blockers (ARB) cause decreased
efferent vessel constriction and put the kidney
at risk of injury in low renal perfusion states
(Longo
et
al.,
2012).
Nonsteroidal
anti-inflammatory drugs (NSAIDs) may also
decrease perfusion, leading to prerenal failure
(Lamiere, Biesen, and Vanholder, 2005).
Metabolic processes of the kidney are
oxygen-dependent; therefore, any interruption
of the flow of oxygenated blood to nephrons
386
makes the kidney susceptible to ischemic
injury.
Table 7.2 Etiologies of prerenal injury.
Intravascular volume depletion
Dehydration
Hypovolemic shock
Hemorrhage
Burns
Diuretic overuse
Gastrointestinal losses
Diaphoresis
Fluid shift to third space
Ascites
Decreased cardiac output
Heart failure/cardiogenic shock
Myocardial infarction
Cardiomyopathy
Dysrhythmias
Thrombus (pulmonary embolism, arterial or
venous thrombus)
Vasoactive medications
Decreased systemic vascular resistance
Sepsis/septic shock
387
Anaphylaxis
Neurogenic shock
Antihypertensive medication overuse
Liver failure
Multiple organ dysfunction syndrome
Anesthesia
Other
Vasculitis
Eclampsia
Disseminated intravascular coagulation
Tumor
Renal artery stenosis
Nonsteroidal anti-inflammatory drugs
Decreased renal perfusion leads to a reduction
in glomerular filtration rate (GFR) and
increased sodium and water reabsorption. As
the GFR decreases, less oxygen is required since
the overall filtration of sodium chloride is
reduced. The filtration of sodium chloride
contributes to most of the consumption of
oxygen and energy produced by the kidney.
Prerenal failure is reversible as long as the renal
blood flow does not decrease to less than
20–25% of normal and damage to the renal
cells has not occurred. As the GFR approaches
zero, renal oxygen consumption is minimized to
388
the point needed to keep renal cells alive.
Prerenal failure is reversible with early
intervention to restore renal perfusion but
otherwise it will progress to intrinsic injury
within a few hours (Hall, 2011).
Intrarenal injury
Intrarenal, or intrinsic injury, is due to
structural damage to the glomerulus, vessels, or
kidney tubules. Intrinsic injury is caused by
ischemic, nephrotoxic, or inflammatory factors
(Carlson, 2009). Table 7.3 summarizes the
etiologies of intrarenal failure.
Table 7.3 Common causes of intrarenal failure.
Ischemic
Shock
Renal artery thrombosis
Prolonged hypoperfusion
Excessive fluid losses
Sickle cell disease
Nephrotoxic
Medications (such as aminoglycosides,
amphotericin B, tetracyclines, vancomycin,
rifampin, penicillins, cephalosporins,
quinolones, sulfonamides, chemotherapeutic
agents, anesthetic agents)
Radiographic contrast dye
389
Pesticides
Fungicides
Ethylene glycol
Heavy metals (such as mercury and lead)
Carbon tetrachloride
Myloglobin
Hemoglobin
Uric acid
Myeloma light chain proteins
Inflammatory
Vasculitis
Glomerulonephritis
Acute pyelonephritis
Blood transfusion reaction
Allergic nephritis
Acute tubular necrosis
Acute tubular necrosis (ATN) is the most
common cause of intrinsic injury (Lamiere,
Biesen, and Vanholder, 2005). In the critical
care unit, 35–50% of all ATN is caused by
sepsis, and 20–25% of ATN is associated with
surgery. Postoperative ATN is often a
consequence of preexisting renal impairment,
hypertension, cardiac disease, peripheral
390
vascular disease, diabetes mellitus, jaundice, or
advanced age. Radiocontrast nephropathy
accounts for the third most common cause of
ATN in hospitalized patients (Lamiere, Biesen,
and Vanholder, 2005).
Conditions that impair blood flow to the kidney
impede the delivery of oxygen and nutrients to
renal cells. If adequate blood flow is not
restored, epithelial cells in the tubules begin to
die. The sloughing off of the dead epithelial
cells fills the tubules with debris and impedes
urine flow. Oliguria, which may evolve to
anuria, along with electrolyte imbalance and
acidosis, will develop (Hall, 2011).
A variety of medications or toxins may induce
ATN. The large volume of blood that is filtered
through the kidneys results in increased
susceptibility to damage as blood is filtered and
filtrate is reabsorbed. Moreover, the generation
of toxic metabolites from certain medications
makes the kidneys vulnerable to injury
(Carlson, 2009). Renal cells are destroyed
through
various
mechanisms
including
vasoconstriction, direct damage to tubular cells,
or intratubular obstruction (Yaklin, 2011).
Regardless of the cause, epithelial cells slough
from the basement membrane, causing
plugging of the tubules. New tubular epithelial
cells can grow along the basement membrane
allowing the tubule to heal within 10–20 days
as long as the agent that precipated the damage
391
is removed and there is no further injury to the
kidney (Hall, 2011).
Radiographic contrast agents are particularly
nephrotoxic to the kidneys if preexisting kidney
disease is present (Longo et al., 2012).
Preexisting chronic kidney impairment makes
the kidney more vulnerable to injury to
contrast-induced
nephropathy
(CIN).
Conditions such as diabetic nephropathy,
chronic low cardiac output states, and multiple
myeloma (Longo et al., 2012) place patients at
risk. Other risk factors for CIN include age
greater than 70 years, dehydration, heart
failure, and concurrent use of nephrotoxic
agents (Naughton, 2008). If an AKI is caused
by radiographic contrast agents, it usually
evolves within 3 days after administration.
Creatinine typically begins to increase within 24
h and peaks in 5 days (Bentley, Corwin, and
Dasta, 2010).
Acute intersitial nephritis
Acute interstitial nephritis (AIN) is caused from
NSAIDs, antibiotics, and other agents (Yaklin,
2011). AIN is believed to be the result of an
allergic response to the suspected drug, and is
not dose-dependent. In the kidney, medications
causing AIN may bind to antigens or act as
antigens that are deposited into the
interstitium, causing a hypersenitivity reaction.
Typical symptoms of an allergic response, such
as fever, rash, and release of eosinophils, are
392
not usually reported (Naughton, 2008). Table
7.4 lists common drugs that may cause AIN.
Table 7.4 Drugs causing acute interstitial
nephritis.
Adapted from Naughton (2008).
Allopurinol
Antibiotics
Beta lactams
Quinolones
Rifampicin
Sulfonamides
Vancomycin
Antivirals
Acyclovir
Indinavir
Diuretics
Loop
Thiazide
NSAIDs
Phenytoin
Proton pump inhibitors
Omeprazole
Pantoprazole
393
Allopurinol
Lanoprazole
H2 Blockers
Ranitidine
Progression of AIN has three stages including
initiation, maintenance, and recovery (Yaklin,
2011). It is important to keep in mind that all
patients do not progress to the recovery stage,
and the end result for that group of patients is
chronic renal insufficiency or end-stage renal
disease. During the initiation phase, blood urea
nitrogen (BUN) and creatinine increase.
Urinary output declines but not all patients
progress to anuria. The maintenance phase
usually lasts about 7–21 days, and often renal
replacement therapy is required during this
phase to maintain fluid, electrolyte, and
acid–base balance. The recovery phase begins
when there is a significant increase in urinary
output and a decline in BUN and creatinine. As
the epithelial cells in the tubules regenerate, the
kidneys regain their ability to concentrate urine
and maintain adequate electrolyte and
acid–base balance (Yaklin, 2011).
Post renal injury
Post renal injury is caused by a partial or
complete obstruction of urine flow at any point
in the urinary drainage pathway from the
394
kidney to the urethra. The cause of the
obstruction may be from blood clots, calculi,
strictures, benign prostatic hypertrophy,
malignancies, or pregnancy (Yaklin, 2011).
Other factors such as fibrosis, neurogenic
disorders, or even urinary catheter obstruction
can contribute to post renal injury. The amount
of damage to the kidneys is determined by the
location, duration, and amount of obstruction
(Carlson, 2009).
When urinary flow becomes obstructed, the
ureters and renal pelvis dilate. Eventually,
intratubular pressure will exceed glomerular
pressure. Complete obstruction causes a
complete cessation of filtration, while a partial
obstruction will decrease GFR but may not
necessarily cause a total cessation of filtration.
The tubules will respond by increasing water
and sodium reabsorption. If the obstruction
continues, the tubules become damaged and are
unable to reabsorb water and sodium. If the
obstruction is not corrected or removed,
permanent renal damage can result (Carlson,
2009; Yaklin, 2011). If the obstruction is
removed or corrected, a post-obstructive
diuresis will occur during the next 24 h if the
damage has not progressed to end-stage renal
disease (Yaklin, 2011).
Monitoring elements
Specific diagnostic tests or physical assessment
findings do not conclusively indicate AKI. A
395
thorough patient history, physical examination,
interpretation of laboratory, ultrasonographic,
and radiological data all provide important
information that contributes to the diagnosis
(Bentley, 2011).
History and physical assessment
A thorough patient history and physical
assessment findings are important for the
diagnosis of AKI. Patient history should include
both family and past medical history. Family
history should examine any genetic factors that
could contribute to AKI such as tubular
metabolic anomalies, polycystic kidneys,
unusual types of nephritis, or vascular or
coagulation defects. Patient history includes
any possible conditions of past or recent kidney
injury such as infections, injuries, exposure to
toxic agents or drugs, diabetes mellitus,
hypertension, or autoimmune disorders that
may make the patient more susceptible to AKI
(Vincenti and Amend, 2008).
Physical assessment findings of AKI are often
related to the etiology (Table 7.5). Prerenal
failure is caused by hypovolemia, decreased
systemic vascular resistance, or insufficient
cardiac output. Assessment findings from
hypovolemia
may
include
tachycardia,
hypotension, flat neck veins, dry mucous
membranes, and decreased mental status. On
the other hand, physical assessment findings
from decreased systemic vascular resistance
396
reveal signs similar to hypovolemia although
systemic edema may be present (Carlson,
2009). The patient may be total body fluid
overloaded but intravascularly depleted due to
third spacing of fluid. If prerenal failure is from
decreased cardiac output caused by cardiac
failure, assessment findings such as oliguria,
edema, distended neck veins, and hypotension
are common.
Table 7.5 Physical assessment findings in
prerenal failure.
Adapted from Carlson (2009).
Hypovolemia/decreased
intravascular resistance
Decreased
cardiac
output
Oliguria
Oliguria
Tachycardia
Tachycardia
Hypotension
Hypotension
Flat neck veins
Distended neck
veins
Dry mucous membranes
Decreased mental status
Physical assessment findings for intrarenal
failure are dependent upon the etiology. If the
cause is ischemic from hypoperfusion, the signs
are similar to the findings of hypovolemia or
decreased intravascular resistance due to
prerenal failure (Carlson, 2009). If failure is
397
from other causes, signs such as oliguria or
anuria, edema, distended neck veins, and other
signs of fluid overload and deterioration of
mental status may be noted.
Post renal failure physical assessment findings
reveal anuria along with signs of fluid overload.
The extent of fluid overload depends on the
length of time and amount of fluid intake while
the obstruction is present.
Laboratory analysis and data trending
Alterations in urine volume, urine specific
gravity, urine osmolality, serum BUN, serum
creatinine, serum BUN/creatinine ratio, urine
sodium, and the fractional excretion of sodium
(FENa) are laboratory studies that provide data
for the practitioner to diagnose AKI and its
etiology (Table 7.6).
Table 7.6 Differential laboratory diagnosis of
renal dysfunction.
Adapted from Carlson (2009, p. 890).
Normal
Prerenal Intrarenal Postrenal
Urine
volume
1–1.5 l/day
<400 ml/ <400 ml/
day
day
Urine
specific
gravity
1.010–1.020 1.020 or
greater
Urine
500–850
osmolality mOsm/l
>500
Osm/l
398
Variable
Fixed
(1.010 or
less)
Fixed
(1.010 or
less)
<350
mOsm/l
≤350
mOsm/l
Normal
Serum
BUN
Prerenal Intrarenal Postrenal
10–20 mg/ >25 mg/
dl
dl
>25 mg/dl
<25 mg/dl
Serum
0.8–1.2 mg/ Normal to >1.2 mg/dl >1.2 mg/dl
creatinine dl
slightly
elevated
Serum
10:1
BUN:
creatinine
ratio
20:1 or
greater
(10–15):1;
both
elevated
but ratio
remains
constant
Urine
sodium
<20
mEq/l
>40 mEq/l >40 mEq/l
FENa
<1%
>1%*
*When the patient is not under the influence of
diuretics.
BUN, blood urea nitrogen; FENa, fractional
excretion of sodium.
Electrolyte imbalances are also a common
finding in AKI. Of particular concern to the
practitioner
is
the
development
of
hyperkalemia, which, if not promptly acted
upon,
may
result
in
life-threatening
dysrhythmias. Signs of hyperkalemia include
decreased reflexes, tachycardia, confusion,
hypotension, anorexia, muscle weakness, and
paresthesia. Electrocardiogram (ECG) changes
associated with hyperkalemia are peaked T
399
(10–15):1;
both
elevated
but ratio
remains
constant
>1%
waves and widened QRS complexes. If not
appropriately treated, ventricular fibrillation
may result (Lippincott Manual of Nursing
Practice, 2007). Other electrolytes that may be
affected by AKI are sodium, magnesium,
calcium, and phosphate. Table 7.7 lists
electrolyte imbalances related to AKI.
Table 7.7 Electrolyte imbalances related to
AKI.
Compiled from Lippincott Manual of Nursing
Practice Series: Diagnostic Tests (2007).
Calcium
Normal
value
Abnormal Comments
value due
to AKI
Serum
8.2–10
mg/dl
Serum <
8.2 mg/dl
Ionized
Ionized <
4.65–5.68 4.65 mg/dl
mg/dl
Magnesium Serum
1.3–2.1
mg/dl
Serum >
2.1 mg/dl
Phosphate Serum
2.7–4.5
mg/dl
Serum >
4.5 mg/dl
Potassium
Serum >
5.5 mg/dl
Serum
3.5–5.0
mg/dl
400
Sodium
Normal
value
Abnormal Comments
value due
to AKI
Serum
135–145
mg/dl
Variable
Urine sodium
levels are
more sensitive
to changes in
sodium
balance and
should be
monitored
along with
serum sodium
levels. The
administration
of diuretics
makes the
urine sodium
less reliable
The kidneys play an important role in
acid–base regulation. Organic anions, such as
phosphate, begin to accumulate when renal
function is impaired. Bicarbonate production
decreases in the proximal tubules along with
decreased reabsorption. Patients with renal
impairment tend to be hypoalbuminemic,
causing a reduced protein-buffering capacity,
contributing to metabolic acidosis. It is also
important to keep in mind that conditions such
as lactic acidosis, respiratory acidosis, shock, or
401
others may also increase the severity of acidosis
(Carlson, 2009).
Urinalysis is an important tool to diagnose AKI.
The presence of urinary sediment is indicative
of AKI, and provides insight for the practitioner
into its etiology. Table 7.8 outlines urine
findings in AKI.
Table 7.8 Urinary findings in acute kidney
injury.
Reproduced with permission from Yaqub and
Molitoris (2009). © McGraw-Hill.
Etiology
Sediment
Prerenal azotemia Few hyaline
casts
FENa
Proteinuria
Fe-urea
<1–3
None or trace
Ischemia
Epithelial
>2–50
cells,
muddy-brown
casts,
pigmented
granular casts
Trace to mild
Acute interstitial
nephritis
White blood >1
cells (WBCs),
WBC casts,
pigmented
granular casts
Mild to
moderate
Acute
Dysmorphic
glomerulonephritis red blood
402
<1 early Moderate to
severe
Etiology
Sediment
FENa
Proteinuria
Fe-urea
cells (RBCs),
RBC cast
Postrenal
Few hyaline <1 early None or trace
casts, possibly >1 late
RBC
Tumor lysis
Uric acid
crystals
None or trace
Arterial/venous
thrombosis
RBCs
Mild to
moderate
Ethylene glycol
Calcium
oxalate
crystals
Trace to mild
Biomarkers
reveal
changes
at
the
molecular–cellular level that may detect AKI in
its earliest stages (Bentley, 2011). Cystatin C, an
endogenous protease inhibitor measured in the
serum, is a marker of AKI. Cystatin C has
shown promise for identifying AKI 1–2 days
earlier
than
the
RIFLE
criteria
(Herget-Rosenthal et al., 2004). It is produced
at a constant rate by nucleated cells, but not
produced by kidney tubules. While creatinine
values are affected by age, muscle mass, diet,
and sex, cystatin C is not (Dirkes, 2011). When
the tubules are functioning normally, cystatin C
is reabsorbed and eventually metabolized
(Yaqub and Molitoris, 2009). As GFR
decreases, cystatin C levels rise. This marker is
403
considered a more sensitive indicator of AKI,
especially in the elderly (Coca, 2010; Yaklin,
2011) but it is not yet routinely used in most
medical centers.
Other novel biomarkers are now being
evaluated for prediction and early detection of
AKI. Biomarkers that have recently been under
scrutiny are neutrophil gelatinase–associated
lipocalin (NGAL), kidney injury molecule-1
(KIM-1), and interleukin (IL)-18. These
biomarkers are more specific for AKI than
traditional markers and their routine use in the
future is promising.
NGAL protein is detected early in AKI in animal
models (Devarajan, 2011). It is present in the
kidneys, lungs, stomach, and colon at low
levels. Injured epithelium releases NGAL in
conditions such as acute bacterial infections,
asthma, and pulmonary disease. NGAL is
present in both blood and urine more often
than traditional markers in animal models
(Dirkes, 2011). Urine NGAL is a reliable
measure to distinguish between prerenal
azotemia and intrarenal failure and chronic
kidney disease (Nickolas et al., 2008). Studies
have shown that plasma or urinary elevations of
NGAL 1–3 days after cardiac surgery were
associated
with
postoperative
AKI
(Hassse-Fielitz et al., 2009). Urine NGAL
collected on the day of kidney transplant
successfully identified patients who developed
404
delayed graft function and required dialysis
within the first week after transplant (Hall et
al., 2010).
KIM-1 is a transmembrane protein that
becomes unregulated in proximal tubule cells
after
ischemic
or
nephrotoxic
injury
(Devarajan, 2011). KIM-1 appears to be more
specific to ischemic or nephrotoxic injury, and
is not significantly increased in chronic kidney
disease or urinary tract infection (Dirkes, 2011).
Urinary KIM-1 levels have been shown to
predict adverse clinical outcomes and mortality
of patients with AKI (Liangos et al., 2007).
IL-18 is a proinflammatory mediator released in
the proximal tubule after AKI. Urinary levels of
IL-18 increase in ischemic injury (Parikh and
Devarjan, 2008). IL-18 is a marker of AKI in
patients with adult respiratory distress
syndrome (ARDS) and elevated urinary levels
predicted the development of AKI within 24 h.
In addition, the level of IL-18 at initiation of
mechanical ventilation was predictive of
mortality independent of severity of illness,
urine creatinine, and urinary output in one
study (Parikh et al., 2005). While these
biomarkers appear promising, further study is
needed to determine their sensitivity and
specificity to AKI, and to determine if
combinations of these biomarkers at specific
levels are clinically significant (Lamiere, Biesen,
and Vanholder, 2005).
405
Diagnostic imaging
Imaging is an essential part of the diagnostic
work-up for AKI. A renal ultrasound reveals the
size, position, internal structures, and perirenal
tissues. It also detects urinary or perirenal
obstruction. Fluid collections within or around
the kidney can be identified that are indicative
of urinary obstruction. It is important to note
that false negative findings are possible in the
earliest stages of urinary obstruction. Renal
doppler ultrasound can evaluate blood flow to
the kidneys. Abnormal blood flow to the
kidneys can indicate obstruction, hypertension,
or other acute or chronic kidney injury (Yaklin,
2011).
Computerized tomography (CT) scans can be
used to visualize the kidneys and collecting
system, but radiocontrast agents should be
avoided. Without the use of a contrast agent,
visualization of the collecting system may be
suboptimal; CT scans without contrast are
helpful to identify obstructing ureteral calculi
(Sharfuddin et al., 2012). Other diagnositic
imaging that requires radiocontrast agents is
usually avoided to prevent further progression
of AKI. Table 7.9 summarizes diagnostic
imaging findings and their implications.
Table 7.9 Diagnostic imaging in acute kidney
injury.
406
Imaging
Normal
findings
Abnormal
findings
Renal
ultrasound
Kidneys
located
between
the iliac
crests and
diaphragm,
normal
size, shape,
and
structure
Cysts, tumors, May show
hydronephrosis, renal
obstruction of obstruction
ureters, calculi
Renal
Doppler
ultrasound
Normal
blood flow
to both
kidneys
Decreased
blood flow to
one or both
kidneys
Possible
obstruction,
hypertension,
or acute or
chronic kidney
injury
Cysts, tumors,
hydronephrosis,
obstruction of
ureters, calculi
May show
renal
obstruction;
however, it is
useful only if
contrast media
is
contraindicated
Computerized Kidneys
tomography located
(CT) scan
between
the iliac
crests and
diaphragm,
normal
size, shape,
and
urinary
collection
system
407
Implications
Renal biopsy
Renal biopsy is not a first-line diagnostic tool to
idenfy AKI. Prerenal and postrenal causes of
AKI must be first ruled out. Renal biopsy is
used only if the cause of intrarenal failure
cannot be determined. Its use should be limited
to intrinsic renal failure that is not due to
ischemic or nephrotoxic injury (Sharfuddin et
al., 2012). Possible findings from renal biopsy
are
glomerulonephritis,
vasculitis,
or
malignancy (Yaklin, 2011).
Evidenced-based treatment guidelines
At this time, there is no specific treatment for
AKI (Bagshaw et al., 2010; Calzavacca, Licari,
and and Bellomo, 2010; Dirkes, 2011;
Sharfuddin et al., 2012; Yaklin, 2011). The goals
of therapy are to prevent AKI, minimize fluid
and electrolyte imbalance if it should occur, and
prevent uremic complications (Sharfuddin et
al., 2012). Preventative measures should be
rapidly implemented for any critically ill patient
at risk for AKI to prevent renal injury and
complications associated with renal failure.
Strategies to prevent or mitigate AKI must be
individualized for each patient’s unique clinical
situation (Bagshaw et al., 2010).
Prevention
Early recognition of patients at risk is a
first-line intervention to prevent AKI. The
408
RIFLE criteria (Fig. 7.1) present an important
tool to identify patients at risk or those at the
early stages of AKI (Bellomo et al., 2004).
Other risk scales for AKI are available for
patients undergoing procedures such as cardiac
catherization or cardiac surgery (Mehran et al.,
2004; Thakar et al., 2005). Maintenance of
adequate renal perfusion, avoidance of
nephrotoxic drugs, and radiographic contrast
whenever possible are important interventions
for high-risk patients. Careful monitoring of
drug levels has been demonstrated to reduce
the risk of AKI with aminoglycosides (Appel,
1990; Blaser and Konig, 1995). Use of
alternative formulations of nephrotoxic drugs,
such as lipid-encapsulated formulations of
amphotericin B, may prevent drug-induced AKI
(Lamiere, Biesen, and Vanholder, 2005). Drugs
that decrease regulation of renal blood flow,
such as NSAIDs, ACE inhibitors, or
angiotensin-II-receptor blockers, should be
avoided or used cautiously (Sharfuddin et al.,
2012).
Aggressive
intravascular
volume
repletion has been reported to prevent ATN in
patients with major surgery, trauma, and sepsis
(Sever, Vanholde, and Lameire, 2006;
Sharfuddin et al., 2012).
Hemodynamic monitoring
Hemodynamic monitoring is an important tool
to guide resuscitation. Measures such as central
venous monitoring, pulmonary arterial catheter
409
monitoring, or devices that measure stroke
volume and pulse pressure variation should be
considered. The use of hemodynamic
monitoring is to direct intravascular volume
repletion to achieve adequate mean arterial
pressure and cardiac output (Bagshaw et al.,
2010). See Chapter 5 for further discussion on
hemodynamic monitoring.
Volume expansion
Volume expansion is needed to prevent or treat
hypovolemia or renal hypoperfusion caused by
vasodilation and decreased intravascular
resistance. The choice of colloid versus
crystalloids for volume resuscitation remains
controversial. Fluid resuscitation with saline
with or without albumin have similar results in
critically ill patients (Finfer et al., 2004). If the
patient’s hemoglobin is low, blood transfusion
may be considered. Close monitoring of
hemodynamics is essential to prevent fluid
overload from overly aggressive volume
resuscitation. A foley catheter should be
considered to closely monitor urinary output in
response to fluid resuscitation. Macedo et al.
(2011) found that oliguria measured by hourly
outputs significantly predicted AKI sooner even
in patients without elevated serum creatinine,
providing for earlier diagnosis and intervention
in the management of critically ill adults.
Patients who were oliguric for more than 12 h
410
or had multiple episodes of oliguria had higher
mortality in this study (Macedo et al., 2011).
Management of electrolyte and acid–base
imbalance
Hyperkalemia is the most serious electrolyte
imbalance
associated
with
AKI.
Mild
hyperkalemia (serum potassium < 5.5 mEq/l) is
controlled by dietary restrictions of potassium.
Severe hyperkalemia (serum potassium > 5.5
mEq/l) is treated with sodium polystyrene
sulfonate, which enhances intestinal potassium
losses. Loop diuretics, such as furosemide, can
be used in a patient with severe hyperkalemia
to excrete potassium if the patient is still
diuretic responsive. If ECG changes indicative
of hyperkalemia are present, 10–20 units of
regular insulin is administered intravenously to
increase potassium entry into the cell and
decrease serum potassium level. The patient is
also given dextrose, 25–50 g IV to prevent
hypoglycemia caused by the administration of
insulin. Intravenous calcium may also be
administered to antagonize the cardiac and
neuromuscular
effects of hyperkalemia.
Intravenous bicarbonate can be given to
enhance bicarbonate intake into the cell;
however, its effect is not rapid enough to be
clinically significant (Sharfuddin et al., 2012).
411
Clinical Pearls
If dialytic therapy is needed to treat
hyperkalemia, hemodialysis is the most
efficent modality to remove potassium, and is
the preferred method if life-threatening ECG
changes are present.
Hyponatremia, accompanied by a
corresponding fall in serum osmolality, is
treated with water restriction.
Hypernatremia is treated with the
administration of water or hypotonic IV
solutions (Sharfuddin et al., 2012).
Hyperphosphatemia is controlled by
restricting dietary phosphate intake and
administration of a phophate-binding agent.
Common phosphate-binding agents are
aluminum hydroxide, calcium salts,
sevelamer carbonate, or lanthanum
carbonate.
Acidosis is usually not treated unless the
serum bicarbonate is ≤15 mEq/l or the blood
pH is <7.15–7.20. When metabolic acidois is
due to AKI, oral or parenteral bicarbonate
may be administered. Administration of
bicarbonate requires careful monitoring for
undesired effects such as metabolic alkalosis,
hypocalcemia, hypokalemia, hypernatremia,
412
and volume overload (Sharfuddin et al.,
2012).
Pharmacologic interventions
Furosemide is frequently used during various
stages of AKI. A meta-analysis examined the
use of furosemide with AKI and found that it
did not have a direct affect on mortality or
improvement in renal function (Ho and
Sheridan, 2006). Furosemide may be useful to
decrease fluid retention in patients receiving
mechanical ventilation. Patients will respond to
furosemide more favorably in mild versus
severe AKI (Ho and Power, 2010).
In the past, low-dose dopamine was routinely
used as a renal vasodilator to maintain renal
perfusion. Multiple studies revealed that it does
not reduce mortality or contribute to renal
recovery, even when used in combination with
furosemide. In light of the current evidence,
renal dose dopamine should not be used to
prevent AKI (Kellum and Decker, 2001).
The use of N-acetylcysteine (NAC) to prevent
contrast nephropathy is controversial. Its use is
not supported by evidence. NAC may cause a
decrease in serum creatinine concentration that
does not seem to cause a protective effect on the
kidneys (Alonso et al., 2004; Hoffmann et al.,
2004).
413
The management of AKI caused by
decomponsated heart failure may include many
agents. Furosemide may be used with caution.
It may have a favorable response by decreasing
vascular congestion, venous congestion, and
intravascular volume. Care must be taken by
the practitioner to prevent overdiuresis causing
renal
hypoperfusion.
Inotropes
and
vasodilators may also be needed to improve
cardiac
output
and
reduce
afterload
(Sharfuddin et al., 2012).
Vasoconstrictors are used in the setting of
hepatorenal failure. Octreotide and midodrine,
used in conjunction with albumin may improve
renal perfusion. It is recommended that
patients with hepatorenal failure have an
expedited referral for livery transplant
(Runyon, 2009).
Water-soluble vitamins are administered to
patients receiving renal replacement therapy
(Sharfuddin et al., 2012). Calcium carbonate is
administered as needed for hypocalcemia.
Doses of medications often need to be adjusted
if AKI is present. If the patient is receiving renal
replacement therapy, doses need to be adjusted
based on the dialytic therapy used. Consultation
with the clinical pharmacist is helpful to ensure
appropriate medication dosing.
414
Prevention of radiocontrast nephropathy
Prehydration
is
effective
in
reducing
radiocontrast-induced
nephropathy
(Calzavacca, Licari, and Bellomo, 2010) and the
use of 0.9% saline has been found to be more
effective than 0.45% saline (Mueller, Buerkle,
and Buettner, 2002). Intravenous sodium
bicarbonate solutions can also be used to
prevent radiocontrast nephropathy, although
the evidence is conflicting about its efficacy.
Clinical Pearls
The recommended hydration regimen for
hospitalized patients is 0.9% NS or sodium
bicarbonate solutions infused at 1 ml/kg/h
for 12 h before and after the administration
of the radiocontrast agent (Sharfuddin et al.,
2012). Intravenous hydration is more
effective than oral hydration to prevent
radiocontrast nephropathy (Calzavacca,
Licari, and Bellomo, 2010).
Nutrition
Considerations when assessing nutritional
needs of patients with AKI include severity of
AKI, other comobidities present, and whether
or not renal replacement therapies are being
used (Yaklin, 2011). Patients with AKI should
have a complete nutritional assessment and an
415
individualized nutrition plan established.
Protein intake should be based on catabolic
rate, renal function, and dialysis losses.
Electrolyte intake is adjusted based on serial
monitoring of serum electrolyte concentrations.
If the patient is nil per os (NPO) or cannot take
oral nutrition, enteral feeds should be initiated
(Brown, Compher, and Directors, 2010).
Renal replacement therapy
Timing and dosing of renal replacement
therapy (RRT) remains controversial. Little
evidence is available to support a standardized
dose and timing for initiation of RRT to
optimize patient outcomes (Bouchard, Macedo,
and Mehta, 2010). Intermittant hemodialysis
(IHD), continuous renal replacement therapies
(CRRT), sustained low-efficiency dialysis
(SLED), extended daily dialysis (EDD), and
peritoneal dialysis (PD) are dialytic therapies
currently being used in the critical care unit.
IHD, CRRT, and PD are the most common
modalities of RRTs used in the critical care unit
(Carlson, 2009).
Intermittant hemodialysis
IHD is the most effective method to remove
fluid and electrolytes in a short period of time.
The patient’s blood is pumped through a filter
with a semipermeable membrane where the
transfer of fluids, electrolytes, waste products,
416
and other solutes takes place. A counterflow of
dialysate through the filter, outside of the blood
compartment, enhances the removal of solutes
by diffusion. IHD is the most efficient modality
of RRT, and is the treatment of choice for
severe hyperkalemia. Typically, treatments last
3–4 h. The frequency of treatments is based on
individual patient need and usually ranges from
daily to three times per week. Rapid fluid shifts
can decrease cardiac output, decrease renal
perfusion, and delay healing of the injured
kidneys. Anticoagulation is necessary to
maintain the high blood flow required for this
therapy to be efficient. SLED and EDD are
hybrid therapies of IHD. A conventional
hemodialysis machine is used but operated at a
slower rate, and it is better tolerated in
hemodynamically unstable patients.
Continuous renal replacement therapies
The use of CRRT results in a more gradual
dialysis that is better tolerated by the
hemodynamically unstable patient. Fluids,
electrolytes, waste products, and small to
medium-sized
solutes
are
removed.
Arteriovenous or venovenous vascular access is
used based on the therapy being performed.
Venovenous access tends to be less problematic
because blood is pumped through the blood
circuit using a blood pump while arteriovenous
therapies rely on the patient’s blood pressure to
circulate the blood. Arteriovenous therapies
417
require a single lumen catheter in a large artery,
such as the femoral artery, and a single lumen
dialysis catheter in a large vein, such as the
femoral or internal jugular vein. Venovenous
therapies use a dual lumen dialysis catheter
placed in a large vein, such as the femoral or
internal jugular veins. Venovenous therapies
are used more frequently than arteriovenous
therapies. Table 7.10 summarizes available
CRRTs. Blood is circulated through a filter
containing a semipermeable membrane.
Depending on the modality used, dialysate and
replacement fluids may be used to enhance
solute clearance. Dialysate is infused into the
outer compartment of the filter and does not
make contact with blood. Replacement fluid is
infused directly into the blood circuit and mixes
with the blood. Replacement fluids enhance
convective clearance. Because CRRT is a
continuous therapy, rapid fluid and electrolyte
shifts are avoided, giving the injured kidney a
better chance to heal.
Table 7.10 Modalities of CRRT.
Catheter
access
Slow continuous
ultrafiltration
(SCUF)
Method of
fluid and
solute
removal
Fluids
used
Arteriovenous Ultrafiltration None
Venovenous
418
Catheter
access
Method of
fluid and
solute
removal
Fluids
used
Continuous
arteriovenous
hemofiltration
(CAVH)
Arteriovenous Ultrafiltration Replacement
Continuous
arteriovenous
hemodialysis
(CAVHD)
Arteriovenous Ultrafiltration Dialysate
Convection
Adsorption
Diffusion
Adsorption
Continuous
Arteriovenous Ultrafiltration Replacement
arteriovenous
Convection
Dialysate
hemodialfiltration
Diffusion
(CAVHDF)
Adsorption
Continuous
venovenous
hemofiltration
(CVVH)
Venovenous
Continuous
venovenous
hemodialysis
(CVVHD)
Venovenous
Continuous
venovenous
diafiltration
(CVVHDF)
Venovenous
Ultrafiltration Replacement
Convection
Adsorption
Ultrafiltration Dialysate
Diffusion
Adsorption
Ultrafiltration Replacement
Convection
Diffusion
Adsorption
419
Dialysate
Ultrafiltration – the movement of fluid through
a semi-permeable membrane
Diffusion – the movement of solutes from an
area of higher concentration to an area of lower
concentration
Convection – movement of solutes with fluid
through a semi-permeable membrane
Adsorption – binding of solutes to a
semi-permeable membrane
Peritoneal dialysis
PD uses the peritoneal membrane as a
semipermeable membrane. PD is not as
efficient as IHD or CRRT because fluid and
solute removal is less predictable. Dialysate is
infused through a catheter into the peritoneal
space. The fluid and solutes are exchanged
through the peritoneal membrane using
diffusion, osmosis, and filtration. PD is not the
first choice of RRT for the critically ill patient
because its effects are slow to occur and
abdominal surgery or interventions preclude
the use of PD. Fluid management can become
problematic when PD is used for the patient
with ascites. The risk of infection is greater due
to catheter placement in the peritoneal space.
Table 7.11 compares IHD, CRRT, and PD.
Table 7.11 Comparison of renal replacement
therapies.
420
IHD
Advantages
Disadvantages Potential
complications
Efficient
removal of
fluids and
solutes
Requires
Hemodynamic
specialized
instability
equipment and
specialized staff
Fluid and
Hemodynamic Dialysis
electrolyte
instability from disequilibrium
balance can be rapid fluid shifts syndrome
rapidly altered
Treatment is
short and
intermittent
Often requires
heparinization
Electrolyte
imbalance
Difficulties in
maintaining
adequate
vascular access
Fluctuations of
acid–base
balance
Biocompatibility Inadequate
issues related to nutrition
hemodialyzers
Central
line–associated
bloodstream
infection
Bleeding due to
anticoagulation
Air embolism
421
Advantages
Disadvantages Potential
complications
CRRT Large amounts
of fluids can be
infused
without fluid
overload
Less efficient
solute removal
than
hemodialysis
Hemodynamic
instability
Can be used
with
hemodynamic
instability
Potential for
electrolyte
imbalance
Electrolyte
imbalance
Continuous,
gradual fluid
and solute
removal
Increased
responsibility
for critical care
nurse
Central
line–associated
bloodstream
infection
More precise
fluid
management
Does not quickly Bleeding due to
remove
anticoagulation
potassium
Performed by
critical care
nurse
Requires
vascular access
Hypothermia
May require
anticoagulation
Air embolism
Clotting of the
circuit may
occur
Clotting of
circuit
May induce
hypothermia
422
Advantages
Disadvantages Potential
complications
Access
complications
can occur
(clotting,
bleeding,
infection)
423
PD
Advantages
Disadvantages Potential
complications
Simple
equipment
High risk of
infection
(peritonitis,
catheter site
infection)
Requires less
technical
support
Desired effects Hyperglycemia
slower to occur,
inefficient in an
emergency
Rapid
initiation of
treatment
Possible patient Infection/
discomfort
peritonitis
Protein loss
No
Possible
Hypoglycemia
anticoagulation pulmonary
needed
compromise
(due to reduced
diaphragmatic
compliance,
decreased
ventilation)
Vascular access Less predictable Constipation
not required
for fluid removal
Lower risk of
hypotension,
rapid fluid and
electrolyte
shifts
Risk for
hyperglycemia
and
hyperosmolarity
(due to glucose
in dialysate)
424
Advantages
Disadvantages Potential
complications
May be
contradicted by
abdominal
surgery,
adhesions,
abdominal
drains,
abdominal
wounds, or
peritonitis
Prevention and treatment of AKI presents many
challenges to the advanced practice nurse.
Identification of patients at risk is essential to
develop interventions to prevent or minimize
AKI. Interdisciplinary collaboration is key to
ensure safe, proactive patient care. Many
controversies about the care of the patient with
AKI continue to exist and more research is
needed to resolve them. Identification of
patients at risk is essential to develop
interventions to prevent or minimize AKI.
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433
Chapter 8
Monitoring for blood glucose
dysfunction in the intensive
care unit
Laura Kierol Andrews
Yale School of Nursing, Orange, CT., USA
Diabetes management in the ICU
Hyperglycemia in critical care patients is
common, linked to poor outcomes, and can
occur in both diabetic and nondiabetic patients
(Finfer et al., 2012; Merrill and Jones, 2011;
Moghissi et al., 2009). In nondiabetic patients,
this is called critical illness or stress-induced
hyperglycemia and is an adaptive reaction to
provide the brain and central nervous system
with a steady source of energy. Increased
production
of
catacholamines,
cortisol,
glucagon, growth hormone, and cytokines,
along with the production of glucose from
glycogenolysis and glyconeogenesis, contribute
to hyperglycemia in critically ill patients as part
of the stress response; this may also be
enhanced in patients with sleep disorders (Taub
and
Redeker,
2008).
Treatment
of
sleep-disorded breathing in patients with
diabetes improves quality of life and physiologic
434
status (ADA, 2013). Additionally, insulin
resistance, in both hepatic and skeletal muscles
of the critically ill, exacerbates hyperglycemia
(see Fig. 8.1).
Figure 8.1 Potential pathophysiological
associations between sleep disorders and
diabetes.
Reprinted with permission of Sage Publications.
In the critical care unit, risk factors for
hyperglycemia also include preexisting or
undiagnosed diabetes, infection, sepsis, trauma,
shock, hyperalimentation, older age, and the
use of glycogenic drugs such as epinephrine,
steroids, and immunosuppressive agents. The
effects of hyperglycemia, including delayed
wound healing, infection, and end-organ
damage are thought to be related to alterations
in neutrophil and lymphocyte function that
impair immunity and inflammatory processes,
and an increase in the release of fatty acids
435
from lipolysis and oxidative damage and
protein degradation (ADA, 2013; Clement et al.,
2004).
Effects of hyperglycemia
Hyperglycemia is associated with poor
outcomes (including increased morbidity and
mortality) in cardiovascular, neurologic, and
trauma patients. Landmark studies in surgical
and medical intensive care unit (ICU) patients
examined the effects of intensive insulin
therapy (IIT) (glucose = 80–110 mg/dl) versus
usual insulin therapy (glucose levels up to 215
mg/dl) (Van den Berghe et al., 2001, 2006).
Decreased mortality was seen in both studies
with the use of IIT, but administration of
parenteral nutrition and administration of IV
glucose (200–300 g/day) to study subjects
clouded the applicability of the findings.
Current studies have shown that IIT increased
mortality and patients had significantly higher
numbers of severe hypoglycemic events
(glucose < 40 mg/dl) (Finfer et al., 2009;
Griesdale et al., 2009; Wiener, Wiener, and
Larson, 2008). Krinsley and Grover (2007)
found that a single episode of hypoglycemia
increased mortality by 16.4% compared to
patients without any episodes of hypoglycemia.
In the Normoglycemia in Intensive Care
Evaluation and Surviving Using Glucose
Algorithm Regulation (NICE–SUGAR) study
(Finfer et al., 2012), investigators demonstrated
436
that using tight versus IIT glucose targets
(140–180 versus 80–110 mg/dl) resulted in
fewer hypoglycemic episodes and lower 90-day
mortality in the tight target group. The latest
American
Diabetes
Association
(ADA)
guidelines recommend target glucose levels of
140–180 mg/dl and suggest that the lower end
of the range is potentially associated with less
patient risk (ADA, 2013).
Hyperglycemia management
recommendations
National
organizations
have
published
recommendations that target glucose control
levels to be between 140 and 180 mg/dl in most
ICU patients (AACE and ADA, 2009; ADA,
2012). Additional recommendations by the
ADA (2013) include intravenous (IV)
administration of insulin using protocols and
management plans to minimize and treat
hypoglycemic events in critically ill patients.
Noncritically ill patients should have premeal
glucose targets less than 140 mg/dl. In
nondiabetic patients, glucose monitoring
should be considered for high-risk patients and
treatment based on severity of illness (critical
versus noncritical) (ADA, 2013).
Glucose monitoring
The use of insulin therapy to treat
hyperglycemia requires point-of-care (POC)
testing systems that are fast and accurate. POC
437
glucose monitors conduct whole blood testing,
which is less accurate than laboratory plasma
glucose tests by 11%. In anemic patients, falsely
elevated glucose levels from POC testing can
lead to overtreatment. Oxygen tension levels in
the blood can also affect glucose readings if the
POC monitor uses a glucose oxidase method,
with hypoxemia (PO2 < 44 mmHg) falsely
elevating readings and hyperoxygenated
samples (PO2 > 100 mmHg) falsely lowering
readings (Egi, Finfer, and Bellomo, 2011).
Shearer et al. (2009) found that blood glucose
samples from finger sticks and central venous
catheters differed significantly from laboratory
plasma levels, but not from each other.
Although POC testing is faster and less
expensive, caution is warranted when using it
solely as a means to titrate insulin therapy in
critically ill patients. A frequent comparison to
laboratory plasma glucose samples is necessary
until the technology improves.
Carbohydrate administration
Sources of glucose administration must be
assessed when initiating and maintaining
insulin therapy. Common sources, such as
maintenance of IV fluids with dextrose, IV drips
mixed in dextrose, and nutritional supports
such as enteral and parenteral feeds, if not
monitored carefully, can contribute to
hyperglycemia. An example demonstrating this
point is that administering D5NS at 100 cc/h IV
438
results in 120 g of dextrose per day, but only 60
g if the IV rate is decreased to 50 cc/h. Use of IV
solutions
with
dextrose
may
require
adjustments in insulin doses. Additional
sources such as peritoneal dialysis fluid, in
which 75% of the dextrose is absorbed, should
also be included in carbohydrate calculations.
Careful consideration must also be given to
initiating glycogenic medications such as
epinephrine and steroids when assessing
hyperglycemia, and when weaning these
medications, adjustments to insulin dosing can
be anticipated.
Insulin therapy
It is recommended that IV regular insulin
infusions be used in critically ill patients to
guarantee full absorption of doses. ICU
patients, especially those in shock states or with
anasarca, will have erratic absorption from
subcutaneous administration of insulin. The
onset of IV insulin is immediate and its half-life
is 5–17 min, allowing for POC testing in
unstable patients at least every hour. The use of
nurse-driven protocols has shown promising
results in the literature (Holzinger et al., 2008;
Krinsley, 2004; Shearer et al., 2009). Many
institutions have adapted tight glucose control
targets and currently utilize protocols that allow
nurses to manage hyperglycemia (see Fig. 8.2).
439
Figure 8.2 Critical care insulin infusion
protocol (Hospital of Central Connecticut).
For patients on oral or tube-feeding nutrition,
insulin protocols include testing frequency and
administration of insulin coverage (Fig. 8.3). In
addition, as patients stabilize, conversion to less
restrictive insulin-testing protocols is made.
440
Generally, guidelines for fingerstick glucose
(FSG) testing in patients with tube feedings will
be guided by testing every 6 h and for those
who can eat, testing is generally done prior to
meals and at bedtime.
Figure 8.3 Subcutaneous insulin correction
scales for patients on tube-feeding diets.
See Table 8.1 for a guide used at the author’s
hospital which also contains protocol options
for hypoglycemic management based on the
441
POC testing value and the patient’s mental
status.
Table 8.1 Management options for insulin
coverage of fingerstick glucose (FSG) testing
before meals and at bedtime (Hospital of
Central Connecticut).
Check
one
Sensitive
Usual
Resistant
FSG
Dose (SC)
Dose (SC)
Dose (SC)
Premeal
< 70
mg/dl or
bedtime
< 100
mg/dl
Notify HO
and initiate
hypoglycemia
treatment
Notify HO
and initiate
hypoglycemia
treatment
Notify HO
and initiate
hypoglycemia
treatment
151–200 1 unit
mg/dl
2 units
4 units
201–250 2 units
mg/dl
4 units
6 units
251–300 3 units
mg/dl
6 units
8 units
301–350 4 units
mg/dl
8 units
10 units
351–400 5 units
mg/dl
10 units
12 units
>401
mg/dl
Notify HO
Notify HO
Notify HO
442
Patients on oral diets: FSG testing is
before meals and at bedtime
Coverage is with Glulisine (Apidra ©)
Patients on continuous tube feedings:
FSG testing is every 6 h
Coverage is with regular insulin
HO, house officer; SC, subcutaneous.
Once a patient is hemodynamically stable,
taking in a consistent carbohydrate diet (enteral
or parenteral), and is able to predictably absorb
subcutaneous insulin, he or she can be
transitioned to subcutaneous insulin. When
transitioning from IV insulin to oral intake,
conduct the following procedures:
Calculate the total amount of IV insulin given in
the last 24 h.
Give half that amount in basal form (glargine or
detemir).
Give the other half as rapid-acting insuline
(Glulisine, lispro, or aspart) in three divided
premeal doses.
Supplement with rapid-acting insulin sliding
scale as needed (based on premeal glucose
levels).
Discontinue IV insulin 2 h after basal dose is
given.
443
Hypoglycemia management
Prevention and treatment of hypoglycemic
episodes is very important and nurses must be
clear on adopted protocols for monitoring and
treatment. Finer et al. (2012) summarized the
increased risk of death associated with
hypoglycemia in ICU settings. Table 8.2
demonstrates an adopted hypoglycemia
protocol used at the author’s institution in
Connnecticut. The use of guidelines and nurse
driven protocols are increasingly recognized by
the national guidelines (ADA, 2013; Moghissi et
al., 2009).
Table 8.2 Hypoglycemia protocol: options
based on mental status.
Alert and tolerates oral intake
Give 4 oz. cranberry juice or 6 oz. of regular
sodium
Recheck FSG in 15 min
Alert, no oral intake with IV access
25 ml of Dextrose 50% IV push X 1 (1/2
bristojet of 50% Dextrose)
Not alert with IV access
50 ml of Dextrose 50% IV push X 1 (whole
bristojet of 50% Dextrose)
Recheck FSG in 15 min
Not alert without IV access
444
Glucagon 1 mg IM/SC X 1
Recheck FSG in 15 min
Conclusion
Research continues on the most effective
management and safety protocols to treat
critically ill patients with blood glucose
dysfunction. Recent analyses by Mackenzie,
Whitehouse, and Nightingale (2011) may
influence and change the way clinicians think
about glycemic control in critically ill patients.
In an examination of glucose control metrics
that were linked to mortality in critically ill
patients,
Mackenzie,
Whitehouse,
and
Nightingale (2011) found a number of patient
values that were linked to negative outcomes in
four types of critical care units. The three
metrics were variables measuring central
tendancy (average glucose, time-averaged
glucose, hyperglycaemic index, and median
glucose), metrics of variability (e.g., standard
deviation, glycemic lability index, maximum
glucose, coefficient of variation), and a single
metric of hypoglycemia (minimum glucose).
Makenzie et al. (2011) found an independent
association of each category with mortality and
recommend that these categories be studied
further to better define the actual metrics
accountable for the variation in outcomes for
critically ill patients.
445
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Griesdale, D.E., de Souza, R.J., van Dam, R.M.
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glucose management protocol on the mortality
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hypoglycemia in critically ill patients: risk
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(2009) Comparison of glucose point-of-care
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448
Chapter 9
Monitoring for hepaticand GI
dysfunction
Eleanor R. Fitzpatrick
Surgical Intensive Care & Intermediate Care
Units, Thomas Jefferson University Hospital,
Philadelphia, USA
Physiologic guidelines
The gastrointestinal (GI) system comprises the
alimentary canal, beginning at the mouth;
extending through the pharynx, esophagus,
stomach, small intestine, colon, rectum, and
anal canal; and ending at the anus (Linton,
2012). The GI tract spans approximately 30 ft
in length (see Fig. 9.1). It incorporates
structures that are auxiliary organs of the GI (or
digestive) tract including the liver, pancreas,
and gallbladder (Linton, 2012).
449
Figure 9.1 Gastrointestinal tract.
The GI system is responsible for essential
functions including ingestion and propulsion of
food, mechanical and chemical digestion of
food, synthesis of nutrients such as vitamin K,
absorption of nutrients into the blood stream,
and the storage and elimination of
nondigestible waste products from the body
(Linton, 2012). The liver, the gallbladder and its
bile ducts, and the pancreas are called accessory
glands in the GI system. Their function is to aid
digestion through the delivery of bile and
enzymes to the small intestine. The role of the
450
liver is detoxification of chemicals and synthesis
and storage of nutrients (Linton, 2012). The
pancreas performs the endocrine functions of
insulin and glucagon production as well as the
exocrine function of digestive enzyme secretion.
GI dysfunction can result in acute and critical
illness due to a variety of malfunctions within
the hollow tube-like structure of the tract or
within its auxiliary organs. The GI system is
fraught with disorders, potentially requiring
intensive assessment and monitoring.
Gastrointestinal dysfunction
GI dysfunction may first be noted in the
development of metabolic abnormalities when
there is disruption of the normal activities of
digestion and absorption. The major function of
the GI tract is digestion, converting ingested
nutrients into simpler forms carried to the
portal circulation for use in metabolic processes
(Urden, Stacy, and Lough, 2010). The GI
system also has an important role in the
detoxification and elimination of bacteria,
viruses,
chemical
toxins,
and
drugs.
Disturbances within the hepatic and GI systems
or their hormonal and neural controls can cause
critical
illness
complicated
by
severe
derangement in nutritional status (Urden,
Stacy, and Lough, 2010).
GI dysfunction arises from alterations in
normal function within the esophagus
(esophageal varices), the stomach (ulcers,
451
tumor), as well as small and large intestines
(inflammation, ulceration, tumors). The
auxiliary organs of the GI tract may also contain
the onus of severe disease. Pancreatic function
may go awry with the development of
pancreatitis or a malignant or benign tumor.
Patients may fall victim to abnormalities of the
liver with hepatic dysfunction due to end-stage
liver disease (ESLD) from cirrhosis or hepatitis
or due to acute liver failure (ALF). The
numerous functions of the liver cause its
dysfunction to result in a multitude of
metabolic and synthetic abnormalities. Any
significant alteration in any of these functions
can result in critical illness. Bleeding from
esophageal varices may arise as a liver damaged
by alcohol, hepatitis, or other cause of cirrhosis
becomes fibrotic and portal hypertension
ensues. The development of refractory ascites is
not fully understood but it seems that it is due,
in part, to multifactorial causes of inappropriate
sodium and water retention, hypoalbuminemia
with reduced intravascular osmotic pressure,
portal hypertension, and hyperpermeable
capillaries (Smeltzer et al., 2010). Hepatic
encephalopathy is another sequelae of ESLD
that also has a complex pathophysiology. This
phenomenon is thought, in part, to be related to
ineffective conversion of ammonia into urea for
excretion. Ammonia, which crosses the
blood–brain barrier, has sedating neurologic
effects. There are four stages of hepatic
452
encephalopathy, the fourth being
(Smeltzer et al., 2010) (Table 9.1).
Table 9.1 Clinical
encephalopathy.
grades
of
coma
hepatic
From: Sherlock, S. Diseases of the Liver and
Biliary System, Eleventh Edition. Published
Online: 25 OCT 2007. Wiley Online Library
(I) Mild confusion, euphoria, anxiety, or
depression
Shortened attention span
Slowing of ability to perform mental tasks
(addition/subtraction)
Reversal of sleep rhythm
(II) Drowsiness, lethargy, gross deficits in
ability to perform mental tasks
Obvious personality changes
Inappropriate behavior
Intermittent disorientation of time (and
place)
Lack of sphincter control
(III) Somnolent but rousable
Persistent disorientation of time and place
Pronounced confusion
Unable to perform mental tasks
453
(IV) Coma with (IVa) or without (IVb)
response to painfulstimuli
Blunt-force trauma due to motor vehicle crash,
falls, or contact during sports or penetrating
injury due to gunshot wounds or stabbing to the
abdomen can injure underlying GI structures.
Intraabdominal structures can also be
disrupted by gunshot or stab wounds to the
chest, anywhere below the fourth intercostal
space anteriorly and seventh intercostal space
posteriorly (Wiegand, 2011). These injuries can
result in organ disruption with bleeding or
spillage of GI contents into the peritoneal space
with peritonitis.
Gastrointestinal bleeding
GI hemorrhage occurs in the critically ill with
relative frequency. All critically ill patients
should be considered at risk for stress ulcers
and therefore GI hemorrhage. This bleeding can
arise from upper GI sites (upper GI bleeding) or
from lower GI structures (lower GI bleeding).
The ligament of Treitz (see Fig. 9.2) is the
anatomic site of division between the upper and
lower GI tracts.
454
Figure 9.2 Ligament of Treitz.
The most common causes of upper GI bleeding
are peptic ulcers (either gastric or duodenal),
stress-related
mucosal
disease,
and
esophagogastric varices (Urden, Stacy, and
Lough, 2010). Lower GI bleeding is most often
caused by diverticulosis and arterial–venous
malformations.
The assessment of the hepatic and GI systems
includes an extensive review of the patient’s
history as well as a complete physical
examination. A complete evaluation of these
systems may also include a multitude of
laboratory indices and invasive and noninvasive
testing (Urden, Stacy, and Lough, 2010;
Smeltzer et al., 2010).
455
Monitoring elements: nasogastric
decompression
In order to monitor the acutely or critically ill
patient for signs of abnormalities of the GI
system, placing a nasogastric (NG) tube is an
important action to determine and to diagnose
many abnormal conditions of the GI tract.
Placing an NG tube is critical in differentiating
upper from lower GI bleeding. NG aspiration
with saline lavage is beneficial to detect the
presence of intragastic blood, to determine the
type of gross bleeding, to clear the gastric field
for endoscopic visualization and to prevent
aspiration of gastric contents. A grossly bloody
aspirate in the absence of a traumatic
intubation confirms an upper gastrointestinal
bleed (UGIB). Red blood suggests currently
active bleeding, whereas the appearance of
coffee-ground returns suggests recently active
bleeding. A bilious, nonbloody aspirate strongly
suggests that bleeding is distal to the ligament
of Treitz or stopped many hours before (Cappell
and Freidel, 2008b). The patient vomiting
blood or with bloody NG drainage is usually
bleeding
from
a
source
above
the
duodenojejunal junction because reverse
peristalsis is seldom sufficient to cause
hematemesis if the bleeding point is below this
area (Urden, Stacy, and Lough, 2010). Once an
NG tube is placed, the drainage must be closely
scrutinized for bleeding or for conditions that
456
could precipitate bleeding. Normal gastric
drainage is green or gold bilious in color.
The process of testing gastric contents for blood
is an integral assessment criterion when one
suspects GI bleeding, but the bleeding is occult.
Occult blood is not visible to the naked eye. NG
aspirate or vomitus may be tested for occult
blood by obtaining a small specimen, placing it
on a specialized paper surface (of a
commercially available product), and then
treating it with a chemical designed to detect
the presence of blood through specific color
changes identified by the practitioner (Linton,
2012). Additionally, monitoring the stool for the
presence of gross or occult blood can also be
performed with similar technology. A stool
specimen is applied to a commercially available
slide. When hydrogen peroxide or another
commercially available developer is added to
the sample, any blood cells present liberate
their hemoglobin and a bluish ring appears on
the electrophoretic paper. This reading is made
at precisely the 30 s mark after the developer is
added (Nettina, 2010). Though this test is often
used as a screen for colon cancer in the
outpatient setting, such an assessment made in
the critical care unit may provide more
information about the location of a possible
bleeding site and the severity of the bleeding.
457
Evidence-based treatment guidelines
There are no currently published guidelines for
the insertion of an NG tube in the setting of GI
hemorrhage or other GI disorders. However,
this practice is commonplace and frequently
performed. Published guidelines do exist,
however, recommending rapid assessment and
volume resuscitation of the bleeding patient.
These recommendations include the use of
crystalloid and colloid infusion and the
transfusion of blood products when blood loss
is estimated at 30% or more of circulating
intravascular volume. A standardized protocol
for resuscitation should exist in facilities that
treat patients with GI hemorrhage (Scottish
Intercollegiate Guidelines Network [SIGN],
2008). Volume status and hemodynamic
stability should dictate the amount of fluid
transfused. In hemodynamically unstable
patients or patients with large hemorrhage,
boluses of 500 ml of normal saline or lactated
Ringer solution with continuous reassessment
are appropriate. Determining the need for
invasive monitoring should be based on the
clinical presentation and need for close
assessment and management of volume status.
Transfusion of blood products is recommended
in those patients with hemodynamic instability
despite crystalloid resuscitation and in those
with continuous bleeding. A patient’s age,
comorbid conditions, briskness of bleed,
baseline hemoglobin, and hematocrit levels, as
458
well as evidence of cardiac, renal, or cerebral
hypoperfusion should all be taken into
consideration when determining the quantity of
blood to transfuse. Coagulopathic patients may
require platelets or fresh frozen plasma as
appropriate (Kumar and Mills, 2011). To
replace coagulation factors, it is recommended
that for every four units of packed red blood
cells (RBCs) transfused, a patient be given one
unit of fresh frozen plasma (Maltz, Siegel, and
Carson, 2000). A consensus statement
regarding platelet transfusion recommends that
patients with platelet counts in the range of 50
000–90 000 mm3 do not require platelet
transfusion, whereas those with counts less
than 50 000 mm3 and active bleeding may
require transfusion (Conteras, 1998). Clinical
parameters,
including
age,
comorbid
conditions, and severity of bleed, should be
used to determine whether or not platelets
should be administered to thrombocytopenic
patients (Kumar and Mills, 2011).
Gastric pH
The pH of gastric contents may be measured
frequently to assess for an acidic environment,
a risk factor for the development of peptic
ulceration, especially in the at-risk critically ill.
Though the routine monitoring of gastric pH is
controversial, this may be performed to
maintain the pH between 3.5 and 4.5 with
prophylactic agents such as proton pump
459
inhibitors (PPIs), histamine antagonists, or
agents such as sulcrafate, which coat and
protect the mucosa. Intragastric pH studies
have demonstrated that while a pH of more
than 4 may be adequate to prevent stress
ulceration (prophylaxis), a pH of more than 6
may be necessary to maintain clotting in
patients at risk of rebleeding from peptic ulcer.
Some studies have indicated that although
histamine 2 receptor antagonists and PPIs
effectively raise the pH of intragastric fluids to
more than 4, PPIs are more likely to maintain a
pH of more than 6, a factor to consider for
patients in the intensive care unit (ICU) who
are at risk for rebleeding from peptic ulcers
after hemostasis (Fennerty, 2002; SIGN,
2008). Gastric pH measurements can be made
with litmus paper or direct NG tube probes
(Urden, Stacy, and Lough, 2010). In performing
this assessment, the nurse will also be alert for
the presence of obvious bleeding. With the
hypoperfusion of the GI tract in shock, sepsis,
and other serious conditions, the mucosa may
slough and ulcerate, causing bleeding.
Evidence-based treatment guidelines
No published guidelines currently exist
regarding the routine testing of pH of
intragastric contents. The SIGN guidelines
(2008) discuss the controversial issue of
medications used to treat and to prevent UGIB.
The SIGN guidelines, however, do recommend
460
that, in the patient at high risk for a rebleeding
episode due to peptic ulcer disease, PPIs be
used. This class of drugs is more likely to
maintain intragastric pH at a level of 6 or over
to prevent recurrent bleeding (Ali and Harty,
2009; SIGN, 2008).
Clinical Pearls—Patient
Management and Treatment
NG lavage is often performed during an
upper GI hemorrhage event. It is used to
control active bleeding by decreasing gastric
mucosal blood flow and to evacuate blood
from the stomach. Gastric lavage is
performed by inserting a large-bore NG tube
into the stomach and irrigating it with
normal saline or water until the returned
solution is clear. Room temperature lavage is
recommended over cooled or iced lavage
fluid as cold fluids shift the oxyhemoglobin
dissociation curve to the left, decrease oxygen
delivery to the tissues, and prolong bleeding
time and prothrombin time (Waterman and
Walker, 1973). Iced saline lavage lowers core
body temperature, induces shivering, and
results in an increased metabolic rate
(Andrus, 1987). Iced fluid lavage may also
further aggravate bleeding (Gilbert and
Saunders, 1981; Ponsky, Hoffman, and
461
Swayngim, 1980; Urden, Stacy, and Lough,
2010).
Monitoring elements: laboratory tests
for GI bleeding
Laboratory tests may not provide an accurate
and timely assessment of GI bleeding. RBCs
and plasma are lost in equal amounts during a
bleeding episode. The hemoglobin and
hematocrit may be helpful for monitoring
trends during a bleeding episode and should be
assessed on a frequent basis.
Evidence-based treatment guidelines
There
are
no
published
guidelines
recommending the frequency of laboratory data
monitoring but the 2008 guidelines published
by SIGN (2008) do advise practitioners that
blood urea nitrogen (BUN) should be measured
frequently in patients with GI bleeding as a
marker of bleeding extent, with breakdown of
RBCs within the GI tract raising the BUN level
(SIGN, 2008).
Endoscopic procedures
Endoscopic procedures incorporate a flexible
tube (the fiber-optic endoscope) to visualize the
GI tract and to perform certain diagnostic and
therapeutic procedures. Images are produced
462
through a video screen or telescopic eyepiece.
The tip of the endoscope moves in four
directions, allowing for wide visualization. The
endoscope can be inserted via the mouth or the
rectum, depending on which portion of the GI
tract is to be viewed. Capsule endoscopy utilizes
an ingestible camera device rather than an
endoscope (Nettina, 2010). The capsule
endoscopy’s current utilization is in the
ambulatory, outpatient setting, for the most
part, but could gain applicability in the acute
care setting in the future. The scopic procedure
of endoscopic esophagogastroduodenoscopy
(EGD) is the principal diagnostic procedure to
identify the presence of upper or lower GI
bleeding. EGD can accurately identify the site of
bleeding, provide prognostic information about
rebleeding risk, and offer therapeutic potential
(Ali and Harty, 2009). To isolate the source of
bleeding in a patient with an acute bleeding
episode, an urgent fiber-optic endoscopy should
be performed. When performed within 12 h of
the bleeding episode, endoscopy has a 90–95%
accuracy rate (Urden, Stacy, and Lough, 2010).
EGD provides direct visualization of the upper
GI tract including the esophagus, stomach, and
duodenum. It has several diagnostic indications
including the evaluation of dysphagia,
gastroesophageal reflux disease (GERD),
epigastric pain, and GI bleeding (Ali and Harty,
2009; Stonesifer, 2004). The stomach must be
prepared adequately for the endoscopy to be as
accurate as possible. An NG tube should be
463
lavaged with room temperature saline to
evacuate blood and clots prior to the test being
performed. Room temperature lavage is
preferred to ice lavage since cold temperatures
may
potentiate
vasoconstriction
and
suppressed blood supply to an already
potentially ischemic mucosa.
In the case of a nondiagnostic endoscopic test,
there
are
other
radiologic
diagnostic
interventions that can be made. Namely, a
tagged RBC radionucleotide study can be
performed to identify an obscure but dangerous
site of bleeding. Angiography may also be
performed in the setting of a nondiagnostic
EGD. In patients who are actively bleeding at a
site of at least 0.5 ml/min this test may
accurately identify a site of bleeding. A bleeding
rate of less than 0.5 ml/min precludes its
identification by this diagnostic method
(Urden, Stacy, and Lough, 2010). Therapeutic
interventions may also be performed via
endoscopy or angiography. These strategies
may include treatment of esophageal varices or
bleeding ulcers, biopsy, or dilatation.
Endoscopic treatments also include thermal
coagulation, injection therapy, hemostatic clips,
argon plasma coagulation, and combination
therapy. During these diagnostic and at times
therapeutic interventions, the patient is
sedated. It is important to ensure safe
management of the patient undergoing these
procedures and avoid oversedation. This is
464
accomplished
by
adhering
strictly
to
institutional standards for the management of
moderate sedation.
Evaluation of the lower GI tract also
incorporates a scopic procedure for complete
assessment of the GI tract below the ligament of
Treitz. Colonoscopy assesses the mucosa of the
entire colon and frequently the distal terminal
ileum via a flexible, fiber-optic scope. These
scopes have the same capabilities as those used
for EGD but are larger in diameter and longer.
Still and video recordings can be used to
document the procedure and relative findings
(Smeltzer et al., 2010). Through this procedure,
bleeding, masses, strictures, polyps, and other
pathology may be identified and treated as
noted with EGD: with lasers, heat, or uni- or
bipolar coagulation (see Table 9.2).
Table 9.2 Indications for endoscopic and
angiographic therapy in acute upper and lower
GI bleeding.
Bleeding
source
Injection Ablative Mechanical Angiogra
Duodenal
ulcer
X
X
X
X
Gastric ulcer
X
X
X
X
Esophageal
varices
X
X
465
Bleeding
source
Injection Ablative Mechanical Angiogra
Mallory–Weiss X
tears
X
Angiodysplasia X
of the upper or
lower GI tract
X
Colonic ulcer
X
X
X
X
X
Esophagogastroduodenoscopy is the procedure
of choice for the diagnosis and therapy of upper
gastrointestinal bleeding lesions. Endoscopic
therapy is indicated for lesions with high-risk
stigmata of recent hemorrhage, including active
bleeding, oozing, a visible vessel, and possibly
an adherent clot. Use of these therapies is
dictated by personal experience, training,
preference, cost, and availability (Cappell and
Friedel, 2008b).
Colonoscopy and angiography are diagnostic
and therapeutic interventions. Injections, as
well as ablative and mechanical interventions,
are performed via scopic guidance. Once
bleeding sites are identified angiographically,
vessels may be embolized with coils, fat,
gelfoam, or other commercially available
products. Potent vasoconstrictors such as
vasopressin may also be administered to
coalesce vessels and eradicate bleeding.
466
X
Injection therapy may include use of
epinephrine
or
commercially
available
sclerosants such as sodium tetradecyl sulfate,
polidocanol, or ethanol.
Ablative therapy may include electrocautery,
heater probe, or argon plasma coagulation.
Mechanical therapy may include endoclips or
banding (EVL endoscopic band ligation).
All
three
therapies
are
effective
as
monotherapies, but combined therapies may
increase the efficacy.
If colonoscopy does not yield a diagnostic or
therapeutic result, angiography may be used to
identify the bleeding site (if there is still active
bleeding of 0.5 ml/min) and to correct via
embolization with fat, coils, gelfoam, or other
commercial products. The colon must be
adequately prepared with the use of laxatives or
enemas prior to the patient undergoing the
study. The use of moderate sedation by trained
nursing or anesthesia personnel affords the
patient needed comfort during the procedure
and avoidance of oversedation. See Table 9.3
for other monitoring priorities for intra- and
postendoscopic therapy.
Table 9.3 Monitoring priorities for intra- and
postendoscopic therapy.
Provide patient and family education
regarding the procedure, intra- and
467
postprocedure care. Ensure proper consents
have been obtained.
Elevate head of bed, monitor for aspiration in
patients at risk due to moderate sedation.
Monitor for respiratory depression with use of
moderate sedation.
Ensure patency of venous access. Monitor for
signs of overt and obscure bleeding, continue
volume resuscitation as needed.
Close monitoring of vital signs, cardiac
rhythm, and pulse oximetry. Monitor for
bradydysrhythmias during passage of the
endoscope.
Evidence-based treatment guidelines
Currently published guidelines for the
evaluation and treatment of upper or lower GI
hemorrhage include treatment of patients in a
critical care unit (with at least hourly
monitoring of vital signs) and prompt and
aggressive
stabilization
with
volume
resuscitation.
All
nonsteroidal
anti-inflammatory drugs (NSAIDs) and aspirin
should be discontinued. Early EGD or
colonoscopy (within 24 h of initial
presentation) is also recommended for
diagnosis and therapeutic interventions. It is
also recommended that patients experiencing
an upper GI bleeding episode be evaluated for
the presence of Helicobacter pylori either
468
during EGD biopsy or with a urea breath test.
Patients who test positive for H. pylori should
receive a course of antibiotic therapy. Patients
with GI bleeding due to peptic ulcer disease
should receive pharmacotherapy in the form of
PPIs (Adler, 2004; SIGN, 2008). Intestinal
resection
or
subtotal
colectomy
is
recommended for the management of colonic
hemorrhage
uncontrolled
by
scopic
interventions (SIGN, 2008).
Evidence-based treatment guidelines for
stress ulcers
The published guidelines of the Eastern
Association for the Surgery of Trauma for stress
ulcer prophylaxis mirror other organizations’
recommendations for this effort, especially in
the realm of critical care where patients are at
greatest risk for the development of
stress-related GI bleeding (Guillamondegui et
al., 2008). These recommendations state that
all critically ill patients with associated risk
factors should receive chemical prophylaxis for
stress ulceration. All agents (with the exception
of antacids) appear equally adequate for
prophylaxis against stress ulceration. The agent
of choice is an individual hospital decision. The
duration of treatment is ill-defined but should
be maintained while risk factors are present.
There is insufficient evidence to warrant
cessation of prophylaxis in the setting of enteral
nutrition (Guillamondegui et al., 2008).
469
Clinical Pearls—Patient
Management and Treatment
It is critical in the postprocedure phase of
patient care to evaluate the patient for the
development of a GI perforation, a possible
complication of any scopic procedure. A
perforation is a break in the wall of the
stomach, duodenum, or colon that permits
digestive fluids or stool to leak into the
peritoneal cavity, causing inflammation of
the peritoneum (peritonitis) (Linton, 2012).
Monitoring of the patient’s vital signs and a
thorough assessment for the development of
sudden, sharp epigastric or abdominal pain,
guarding, rigidity, point and/or rebound
tenderness provides the practitioner with a
raised index of suspicion for the onset of a GI
perforation (stomach, duodenum, colon,
etc.). Perforation of the GI tract may also
result in other symptoms. The rapid
evaluation with an abdominal radiograph will
aid the practitioner with this diagnosis and
allow for rapid scopic or surgical
intervention. The practitioner’s initial
management initiative is to use gastric
decompression, intravenous fluids, and
antibiotic agents. A small perforation may
seal spontaneously (Linton, 2012).
470
Monitoring elements: gastric
tonometry and capnometry
Blood supply and tissue oxygenation of the GI
tract is provided via the splanchnic circulation.
When blood flow is decreased due to many
disorders, such as in the shock state, the gut
may be utilized to provide needed information
in assessing for early and accurate warning of
tissue hypoperfusion. Oxygenation of the GI (or
splanchnic) organs can be quantified using
gastric tonometry, which is based upon the
knowledge that when oxygen supply to the
stomach decreases, anaerobic metabolism in
gastric cells produces the by-products of excess
hydrogen ions, lactate, and carbon dioxide. As
gastric carbon dioxide (CO2) levels increase,
hypoperfusion is likely occurring. Gastric
tonometry is a monitor of gastric mucosal
hypoperfusion
and
resultant
hypoxia.
Measurement of the adequacy of the splanchnic
circulation may be particularly important in the
critically ill or injured patient. Splanchnic
hypoperfusion occurs early in shock, and may
occur before the usual indicators of shock such
as hypotension or lactic acidosis are present
(Marik, 2001). Currently available methods of
monitoring gastric CO2 include gastric
tonometry and sublingual capnometry. Gastric
tonometry (see Fig. 9.3) is useful for
monitoriing the difference between gastric and
arterial CO2. A widening gap indicates
471
compromised blood flow to the splanchnic bed,
acidosis, and impaired cellular function
(Johnson, 2005). In gastric tonometry, the
practitioner withdraws samples of saline placed
in the balloon of a specially designed NG tube
and sends the saline and an arterial blood gas to
the laboratory for analysis of CO2 and
bicarbonate (HCO3) concentrations. These
results are used in the Henderson–Hasselbach
equation to determine intramucosal pH (pHi)
(Carlesso, Taccone, and Gattinoni, 2006;
Marshall and West, 2004; Urden, Stacy, and
Lough, 2010). Newer technology known as air
tonometry allows for automatic specimen
withdrawal (of air within the balloon, not
saline) and analysis of pHi (Carlesso, Taccone,
and Gattinoni, 2006; Marshall and West, 2004;
Urden, Stacy, and Lough, 2010).
472
Figure 9.3 Gastric tonometry.
Another assessment tool for the GI tract that
evaluates regional perfusion and oxygenation
has been developed utilizing gastric tonometry
principles. Researchers have demonstrated that
the very proximal GI tract, namely, the tongue
and/or sublingual mucosa, may serve as
appropriate sites for measurement of tissue
CO2. Sublingual capnometry or capnography
was developed to overcome some of the
limitations of gastric tonometry. This
473
noninvasive and portable testing measure
provides data that correlates well with gastric
oxygen (O2) levels (Johnson, 2005). Sublingual
capnometry is a measurement of the CO2 level
in the vascular bed underlying the tongue,
measured in a manner similar to an oral
temperature. SlCO2 has been demonstrated to
be a sensitive marker of splanchnic perfusion
(an early indicator of hypoperfusion) and gut
ischemia. Researchers have demonstrated an
increase in sublingual PCO2 (PslCO2) that was
closely related to decreases in arterial pressure
and cardiac index during circulatory shock
produced by hemorrhage and sepsis (Marik,
2001). Studies in trauma and nontrauma
patients have indicated that SlCO2 may be a
predictor of organ dysfunction, injury severity,
and mortality (Strehlow, 2010).
Widespread adoption of sublingual capnometry
monitoring in areas such as Emergency
Departments has been limited by the
requirement for new equipment, difficulties
with
obtaining
accurate,
reproducible
measurements, and the need for further study
(Strehlow, 2010). Though gastric tonometry
and sublingual capnometry are not widely used,
they should be considered extremely innovative
bedside tools for assessing for decreased tissue
perfusion. Their use may also be of advantage
in assessing patient response to therapy such as
volume resuscitation with crystalloid but
474
further investigation is needed to determine the
role of these technologies.
Evidence-based treatment guidelines
No evidence-based treatment guidelines have
been established to date for the use of routine
gastric tonometry and sublingual capnometry.
Radiographic diagnostics
Plain radiographic films play an important role
in evaluating the critically ill patient for GI
abnormalities. A likely application for this
testing is in the patient with abdominal pain.
Optimally two views of the abdomen should be
obtained for the most thorough evaluation.
Air–fluid levels may be assessed as well as an
evaluation for the presence of free air,
indicating perhaps a perforated viscus. Other
disease states may be evaluated by plain
radiographic films including small or large
bowel obstruction or paralytic ileus, all
resulting in distended loops of bowel evident on
the exam. The addition of contrast to the study
allows for assessment of filling defects and
mucosal abnormalities along the entire GI tract
(Stonesifer, 2004).
Evidence-based treatment guidelines
Many experts dispute the use of the plain
abdominal radiograph in the diagnosis of GI
disorders, particularly in vascular emergencies
475
of the GI tract. However, the general consensus
has been and will continue to be (at least for the
foreseeable future) that this is an easily and
rapidly performed test, which is advantageous
in identifying the presence of a perforated
viscus or intestinal obstruction. It can be
completed without prolonging time to the
operating room for definitive treatment of
intestinal infarction and other conditions
(Cappell and Batke, 2008; Shanley and
Weinberger, 2008). The Royal College of
Radiologists (RCR) recommends the use of
plain abdominal radiography in many acute
conditions of the abdomen including acute
abdominal pain, large or small bowel
obstruction,
pancreatitis,
foreign
body
ingestion, and blunt or stab wound injury to the
abdomen (Smith and Hall, 2009).
Ultrasonography
Abdominal ultrasound and, in particular,
focused abdominal sonography in trauma
(FAST) are important tools in critical care and
gastroenterology. They allow for the evaluation
of liver size and texture, important factors
associated with cirrhosis or fatty liver
infiltration. They may also detect masses and
ascites as well as abnormalities indicative of
cholecystitis. FAST is the mainstay of diagnosis
in patients sustaining blunt abdominal trauma.
It allows for rapid, noninvasive detection of free
fluid within the abdominal cavity and, if found,
476
is an indication for surgical intervention. FAST
may also identify solid organ injuries but its
sensitivity for this assessment is less than that
for fluid. If FAST results are inconclusive for
injury, computed tomography (CT) of the
abdomen may be performed (Stonesifer, 2004).
Evidence-based treatment guidelines
The American Institute of Ultrasound in
Medicine (AIUM) and the American College of
Emergency Physicians (ACEP) state that the
FAST examination is a proven and useful
procedure for the evaluation of the injured
patient immediately during resuscitation to
detect large abnormal fluid collections, which
require immediate treatment. The FAST
guideline includes indications for performing
the examination, qualifications of the
performing practitioner, specifications for
individual
examinations,
documentation
requirements, quality control, and patient
safety standards (Bahner, 2008). Table 9.4
provides a summary of the FAST guideline.
Table 9.4 FAST guideline summary for
abdominal ultrasonography.
Source: Bahner (2008).
Indications/
Patient safety
contraindications standards
Indications for an
ultrasound
477
Indications/
Patient safety
contraindications standards
examination of the
abdomen and/or
retroperitoneum
include but are not
limited to the
following:
Abdominal trauma
The request for the
examination must be
originated by a physician
or other appropriately
licensed health-care
provider or under their
direction.
Abdominal, flank,
and/or back pain
The accompanying
clinical information
should be provided by a
physician or other
appropriate health-care
provider familiar with
the patient’s clinical
situation and should be
consistent with the
relevant legal and local
health-care facility
requirements.
Search for the
For evaluating peritoneal
presence of free or spaces for bleeding after
loculated peritoneal traumatic injury,
particularly blunt
478
Indications/
Patient safety
contraindications standards
and/or
trauma, the examination
retroperitoneal fluid known as focused
abdominal sonography
for trauma (or focused
assessment with
sonography for trauma)
may be performed.
479
Indications/
Patient safety
contraindications standards
Follow-up of known
or suspected
abnormalities in the
abdomen and/or
retroperitoneum
The objective of the
examination is to
analyze the abdomen for
free fluid.
Images should be
obtained in the right
upper quadrant through
the area of the liver with
attention to fluid
collections peripheral to
the liver and in the
subhepatic space.
Images should be
obtained in the left
upper quadrant through
the area of the spleen,
with attention to fluid
collections peripheral to
the spleen. Images
should be obtained at
the periphery of the left
and right abdomen in
the areas of the left and
right paracolic gutters
for evidence of free fluid.
Images of the pelvis are
obtained to evaluate free
pelvic fluid.
480
Indications/
Patient safety
contraindications standards
Analysis through a
fluid-filled bladder
(which if necessary can
be filled through a Foley
catheter when possible)
may help in the
evaluation of the pelvis.
481
Indications/
Patient safety
contraindications standards
All ultrasound
studies of the
abdomen
Adequate
documentation is
essential. There should
be a permanent record of
the ultrasound
examination and its
interpretation. Images of
all appropriate areas
should be recorded.
Variations from normal
size should be
accompanied by
measurements. Images
should be labeled with
the patient
identification, facility
identification,
examination date, and
side (right or left) of the
anatomic site imaged.
An official interpretation
(final report) of the
ultrasound findings
should be included in the
patient’s medical record.
Diagnostic information
should be optimized
while keeping total
ultrasound exposure as
482
Indications/
Patient safety
contraindications standards
Equipment performance
monitoring should be in
accordance with the
AIUM Standards and
Guidelines for the
Accreditation of
Ultrasound Practices.
Intraabdominal pressure management
In the patient who has sustained abdominal
trauma or other abdominal visceral catastrophe
such as mesenteric ischemia or severe acute
pancreatitis,
intraabdominal
hypertension
(IAH) and abdominal compartment syndrome
(ACS) may occur. IAH and ACS develop when
the abdominal contents expand in excess of the
capacity of the abdominal cavity, potentially
suppressing organ perfusion and causing organ
dysfunction or failure and increased morbidity
and mortality (Stonesifer, 2004; Wiegand,
2011). Increased pressure within the abdominal
compartment can be caused by bleeding, ileus,
visceral edema, or a noncompliant abdominal
wall. Increased abdominal pressure can
impinge on diaphragmatic excursion and affect
ventilation, often identified by increasing peak
inspiratory pressures when patients are
mechanically ventilated. Additional clinical
manifestations of ACS include decreased
483
cardiac output, decreased urine output, and
hypoxia (Urden, Stacy, and Lough, 2010).
Measurement of bladder pressure and, thus,
indirectly intraabdominal pressure (IAP), is a
useful way to detect IAH as well as the
progression to ACS. Both conditions are
associated with traumatic injury as well as with
other conditions such as intraabdominal
infection and peritonitis, abdominal surgery,
ascites, pancreatitis, and aggressive volume
resuscitation for the management of shock or
cardiopulmonary arrest.
Intraabdominal pressure measurement
There are many approaches to measuring IAP.
The measurement of this pressure via an
indwelling urinary catheter is a reliable method
(Stonesifer, 2004). The measurement of IAP
can be made with equipment readily available
in the critical care setting but commercially
prepared kits designed for this measurement
are also available. Should elevated IAP (20–25
mmHg or greater) accompany clinical
manifestations
of
ACS,
a
surgical
decompressive laparotomy may be performed.
Surgical decompression incorporates opening
of the abdomen followed by a temporizing
coverage of the viscera after the procedure.
There are many options for management of the
open
abdomen
after
decompressive
laparotomy. Coverage with clear sterile dressing
with some absorptive material and/or drains,
484
and use of a vacuum-assisted technique are just
a few of the options for management of the
open abdomen. The wound is then closed by a
delayed primary closure once the cause of the
ACS has resolved or the wound is allowed to
heal by secondary intention and eventual skin
grafting (Urden, Stacy, and Lough, 2010).
Care of the patient after decompressive
laparotomy poses many challenges including
ongoing assessment of the status of the viscera
for viability and close monitoring for bleeding.
Aggressive
volume
resuscitation
and
assessment of patient response is most often
indicated. A clear, sterile covering of the
dressing affords the practitioner the ability to
visualize the viscera under the dressing to
ascertain its color, an indicator of viability.
Large amounts of intraadominal fluid may
drain from the dressing and depending on the
type of wound management system used, the
fluid may be collected in canisters to allow for
accurate assessment of fluid losses. These fluid
losses may be replaced once quantified via
intravenous fluid administration. Of critical
importance is continuing to monitor the IAP so
that rapid identification of the recurrence of
IAH can be made. Should this result from
excess compressive forces of the dressing or
other complicating factors, the patient would
require an urgent removal and reapplication of
the dressing.
485
Assessment of intravascular volume status and
patient response to therapy is an important part
of the management strategy of the patient post
decompressive laparotomy. Several types of
monitoring tools exist to accomplish this task.
Central venous pressure may be monitored on
an hourly basis providing generalized data on
overall fluid balance and providing a line for
delivering large volumes of fluid (Urden, Stacy,
and Lough, 2010). Monitoring heart rate and
blood pressure response and hemodynamics
can aid in the assessment but new technology
provides
the
practitioner
with
added
information (see Chapter 5). Minimally invasive
cardiac output measurement via pulse contour
waveform (derived from an arterial catheter) or
fluid therapy guided by esophageal ultrasound
analysis calculates stroke volume and/or
cardiac output and contractility. Variability in
stroke volume and cardiac output are useful
assessment tools in establishing patient
response to therapy using this technology
(Urden, Stacy, and Lough, 2010). See Chapter
5: Hemodynamic monitoring for additional
guidelines.
Treatment of abdominal
compartment syndrome
When using a urinary catheter to measure IAP,
the practitioner should instill only 25 cc of
saline to distend the bladder prior to clamping
486
and pressure measurement. Higher amounts of
fluid injection have been shown to falsely
elevate the IAP recording (Cheatham et al.,
2007, Malbrain and Deeren, 2006; Malbrain,
Delaet, and Cheatham, 2007; Tiwari, 2006;
Wiegand, 2011). The World Society of the
Abdominal Compartment Syndrome (WSACS)
has published extensive guidelines and
recommendations including a comprehensive
evidence-based medicine approach to the
diagnosis, management, and prevention of
IAH/ACS (Malbrain and Deeren, 2006). This
group has also published consensus definitions
for IAP, IAH, and ACS which up until the point
of the Society’s meeting in 2006 had never been
determined (Malbrain and Deeren, 2006).
Effective management strategies as described
earlier have been implemented in many
institutions based on the education and
research activities provided by the WSACS in an
effort to improve the survival of patients with
IAH and ACS (Malbrain and Deeren, 2006).
Clinical Pearls—Patient
Management and Treatment
IAP should be measured with the patient in
the supine position with the transducer
leveled and zeroed at the iliac crest in the
midaxillary line (Wiegand, 2011) (see Fig.
9.4). The sequelae of liver disease often result
487
in the need for patients to be admitted to the
critical care environment and to undergo a
multitude of intensive diagnostic and
therapeutic interventions.
Figure
9.4
Patient
positioning
intraabdominal pressure measurement.
for
Diagnostics for liver function
In the assessment and management of the
patient with ESLD or ALF, there is an
armamentarium of tools and techniques.
Laboratory evaluation of hepatic function is
performed by measuring liver function tests.
More than 70% of the parenchyma of the liver
may be damaged before these tests become
abnormal. Liver function is measured in terms
of serum enzyme activity, protein levels,
bilirubin, ammonia, clotting factors, and lipids
(Smeltzer et al., 2010). Ultrasound, CT, and
magnetic resonance imaging (MRI) are also
used to identify normal structures of the liver
488
and biliary tree. A radioisotope liver scan may
be performed to assess liver size and hepatic
blood flow and obstruction (Smeltzer et al.,
2010). However, the evaluation of the patient
with ESLD is most often guided by the results
obtained from the performance of a liver
biopsy.
Evidence-based treatment guidelines
Histological assessment of the liver via a liver
biopsy is a cornerstone in the evaluation and
management of patients with liver disease
(Rockey et al., 2009). A liver biopsy is the
removal of a small amount of liver tissue
usually through needle aspiration to examine
liver cells. The most common indication is to
evaluate disorders of the parenchyma.
Therefore,
liver
biopsy
is
currently
recommended for three major roles: (1)
diagnosis, (2) assessment of prognosis (disease
staging), and/or (3) therapeutic management
decisions (Rockey et al., 2009). The
practitioner must monitor for the development
of intra- and postprocedure bleeding and bile
peritonitis as potential serious complications
after liver biopsy as well as for the occurrence of
pain. Liver biopsy can be performed
percutaneously with ultrasound guidance or
transvenously via the right internal jugular vein
to right hepatic vein under fluoroscopic
guidance. Due to the risk of bleeding, the
evidenced-based recommendation of the
489
American Association for the Study of Liver
Disease (AASLD) is that platelet transfusion be
considered when platelet levels are less than 50
000–60 000/ml (Rockey et al., 2009).
Liver support devices
Encephalopathy,
coagulopathy,
and
hemodynamic instability may arise in patients
with chronic liver failure or ALF. For the
patient with ALF, however, these disorders can
be even more life-threatening. As these patients
are treated in the ICU and often await liver
transplantation, they may require the
additional support of liver dialysis to remove
toxins the damaged liver can no longer
metabolize and excrete. Artificial liver support
systems are designed to purify blood by
removing protein-bound and water-soluble
toxins without providing liver synthetic
functions. Currently available systems are
based on albumin dialysis of plasma separation
and filtration. Bioartificial liver support (BAL)
refers to systems that use viable hepatocytes as
components of an extracorporeal device
connected to the patient’s circulation, and thus
have the potential to provide liver function.
They consist of a bioreactor containing
hepatocytes with or without a blood purification
device. Studies examining the role of
extracorporeal liver support systems have
consistently demonstrated an improvement in
hepatic encephalopathy (Sundarum and
490
Shaikh,
2009)
and
other
phenomenon of liver disease.
end-stage
Liver support devices are used in many
specialized facilities and units that manage liver
failure in its chronic and acute (or fulminant)
form. These devices seek to detoxify substances,
and metabolize and synthesize materials when
the liver no longer functions, in particular, in
the patient with ALF. A variety of systems are
available and/or under study such as sorbent
systems that detoxify but have no hepatocyte
replacement. These systems use charcoal or
other adherent particles in an extracorporeal
circuit. Transient improvement of hepatic
encephalopathy may be observed but no
improvement in hepatic function is seen. Other
systems have attempted the use of porcine
hepatocytes in a bioartificial liver (Polson and
Lee, 2005).
Evidence-based treatment guidelines
The last published guidelines for the
management of ALF (Polson and Lee, 2005) did
not recommend the use of currently available
liver support systems outside of clinical trials.
Polson and Lee (2005) also stated that the
future use of liver support systems in the
management of ALF remains unclear. Since the
publication of these guidelines, however,
research and development of such systems has
continued and, recently, the United States Food
and Drug Administration (USFDA) did approve
491
the use of liver support systems for the
management of fulminant liver failure resulting
from drug overdose, drug toxicity, or other toxic
conditions adversely affecting liver function
(Camus et al., 2009). This process is
undertaken as a bridge to liver transplantation
and is performed in an ICU setting,
implemented by a team skilled in the
management of hepatic disorders.
Guidelines for the management of patients with
ALF recommend that these patients be treated
in an ICU in a transplant center as the only
life-saving measure for these patients is often
liver transplantation. These guidelines also
recommend
that
pulmonary
artery
catheterization (as previously discussed) be
considered even in hemodynamically stable
patients to ensure that appropriate volume
replacement has occurred (Polson and Lee,
2005).
Balloon tamponade therapy
Balloon tamponade therapy is a procedure in
which
a
specialized
tube
(e.g.,
Sengstaken–Blakemore, Linton and Minnesota
tubes) is inserted into the patient with ESLD
who is hemorrhaging from gastric or
esophageal varices. The gastric balloon is
inflated with 250–300 cc of air. It is then pulled
snugly against the gastroesophageal junction.
The esophageal balloon is inflated to 20–40
mmHg pressure for tamponade against
492
bleeding esophageal varices. Esophageal
balloon tamponade is useful for control of acute
bleeding because of the direct, constant
pressure that is applied to the varices. Traction
on the tubes, which places constant pressure on
the varices, is essential for effective
tamponading. This may be used for temporary
hemorrhage control. Long-term use has been
implicated in a higher rate of rebleeding and an
increased complication rate. It is recommended
that the balloon not be inflated for more than
24 h. Esophageal necrosis, esophageal rupture,
and tissue necrosis are some of the adverse
effects from tamponade therapy (Baird and
Bethel, 2011). Specialized practitioners caring
for the patient with liver disease undergoing
balloon tamponade therapy monitor the
pressures in the esophageal balloon frequently
(at least every 4 h) and are careful that it does
not exceed 40 mmHg, thus contributing to the
development of complications. Management of
volume resuscitation and blood transfusion are
key factors in restoring the hemodynamic
stability to an acutely bleeding patient.
As balloon tamponade therapy is a temporizing
measure, plans should be made for patients to
have a more definitive procedure to decrease
portal pressure and the risk of bleeding.
Transjugular intrahepatic portosystemic shunts
(TIPS) are placed under radiologic guidance to
create egress for portal blood flow through a
balloon expandable stent to the systemic
493
circulation. This procedure is successful in
reducing
portal
hypertension
and
decompressing varices to control bleeding
(Urden, Stacy, and Lough, 2010).
Evidence-based treatment guidelines
Guidelines have been published by the AASLD
regarding the use of balloon tamponade therapy
(Garcia-Tsao et al., 2007). These guidelines
describe this treatment as very effective in
controlling
bleeding
temporarily
with
immediate control in the majority of patients.
The use of a balloon tamponade, however, is
associated with potentially lethal complications
such as aspiration, migration, and necrosis/
perforation of the esophagus with mortality
rates as high as 20%. According to the AASLD
guidelines (Garcia-Tsao et al., 2007), its use
should be restricted to patients with
uncontrolled bleeding for whom a more
definitive therapy such as a TIPS procedure is
planned within 24 h of placement. Airway
protection is strongly recommended when
balloon
tamponade
therapy
is
used
(Garcia-Tsao et al., 2007). In the American
Association of Critical Care Nurses Procedure
Manual for Critical Care, it is recommended
that the esophageal balloon port pressure be
measured frequently based upon institution
standards and be maintained at 25–45 mmHg
(Wiegand, 2011).
494
The AASLD published practice guidelines for
prevention and management of varices and
variceal hemorrhage in cirrhosis also include
the following recommendations (Garcia-Tsao et
al., 2007):
Use of beta blocker therapy to reduce portal
pressure for the prevention of a first variceal
hemorrhage in patients with medium to
large esophageal varices.
Endoscopic variceal ligation (EVL) as an
alternative to beta blockers for the
prevention of an initial variceal hemorrhage.
Acute variceal hemorrhage should be
managed with vasoconstrictive
pharmacological therapy and variceal
ligation. To prevent recurrent bleeding
episodes, the use of EVL and pharmacologic
agents is recommended.
A TIPS procedure or surgically created
shunts may be used for those who fail
medical therapy.
ICP monitoring in acute liver
failure
As previously described, patients with ALF who
develop encephalopathy have significant
morbidity and mortality. The onset of cerebral
edema and intracranial hypertension is not fully
understood but these are two of the most
495
serious consequences of ALF and can result in
fatal uncal herniation (Polson and Lee, 2005).
The primary purpose of intracranial pressure
(ICP) monitoring in this patient population is to
detect elevations in ICP and reductions in
cerebral perfusion pressure (CPP) so that
interventions can be made to prevent
herniation while preserving brain perfusion.
The ultimate goal of such measures is to
maintain neurological integrity and prolong
survival while awaiting receipt of a donor organ
or recovery of a sufficient functioning
hepatocyte mass (Polson and Lee, 2005).
Evidenced-based treatment guidelines
The AASLD recommends the avoidance of
sedation in the early stages of encephalopathy
(Garcia-Tsao et al., 2007). They also have
stated that as patients progress to higher stages
of encephalopathy, the head of the bed should
be elevated to 30° to decrease ICP. At this stage,
patients should be intubated to protect their
airway. ICP monitoring and frequent
assessment
of
neurological
status
is
recommended to evaluate and aid in the
treatment of intracerebral hemorrhage (ICH).
The guidelines further state that ICH should be
managed
with
hyperventilation
and
short-acting barbiturates may be considered for
refractory ICH (Polson and Lee, 2005).
496
Ascites management
Ascites is another of the life-threatening
sequelae of ESLD. Ascites, the accumulation of
fluid in the peritoneal cavity, develops as a
result of a multitude of contributing factors and
the exact pathophysiology is unknown. Some of
the complex, contributing factors include portal
hypertension, hyperpermeable capillaries with
leakage of lymph fluid, and albumin-rich fluid
from the diseased liver, low serum albumin
levels, and inappropriate sodium and water
retention (Linton, 2012). According to the
published clinical practice guidelines for the
diagnosis of ascites, the initial evaluation of a
patient with ascites should include history,
physical examination, abdominal ultrasound,
and laboratory assessment of liver function,
renal function, serum, and urine electrolytes, as
well as an analysis of the ascitic fluid. A
diagnostic paracentesis should be performed in
all patients with new-onset grade 2 (mild) or 3
(moderate) ascites, and in all patients
hospitalized for worsening of ascites or any
complication
of
cirrhosis
(European
Association for the Study of the Liver, 2010).
These guidelines also address recommended
management strategies for ascites including
those given in Table 9.5.
Table 9.5 Management strategies for ascites.
Source: European Association for the Study of the
Liver (EASL) (2010).
497
Grade 1 mild
ascites—only
detectable
by
ultrasound
Moderate
ascites—evident
by moderate,
symmetrical
distension of
the abdomen
Severe
Refractor
ascites—large ascites
or gross
ascites with
marked
abdominal
distension
No treatment
Restriction of
Large-volume
sodium intake and paracentesis
diuretics
(LVP) followed
by restriction of
sodium intake
and diuretics
(unless patients
have refractory
ascites)
Measuring the abdominal girth and obtaining
daily weights are important elements to
monitor for the patient with ascites. Both these
are markers of the severity of the fluid
accumulation within the abdominal cavity and
these data can assist the practitioner in
assessing the progression of ascites and its
response to treatment (Smeltzer et al., 2010).
498
LVP with
albumin
administra
continuing
diuretic
therapy (if
effective in
inducing
natriuresis
insertion o
transjugula
intrahepati
portosystem
shunt (TIP
and liver
transplanta
Evidence-based treatment guidelines:
paracentesis
Paracentesis is the removal of ascitic fluid from
the peritoneal cavity. This procedure is
diagnostic and therapeutic. The procedure is
indicated when ascites impairs the patient’s
breathing. Paracentesis removes fluid that
impairs full respiratory excursion but it also
removes essential proteins and electrolytes and
provides a portal of entry for pathogens
(Linton, 2012). The procedure may be
performed at the patient’s bedside or under
ultrasound guidance. Paracentesis may result in
the removal of 2–3 l of fluid or more (Linton,
2012). The removal of up to 6 l of fluid is
termed total volume paracentesis (TVP) or large
volume paracentesis (LVP) and is performed for
those patients with refractory ascites whose
ascites reaccumulates quickly. These patients
are often awaiting liver transplantation.
Whenever paracentesis is undertaken, it is
performed slowly since rapid removal of fluid
can result in circulatory collapse (Linton, 2012).
Patients undergoing TVP may require the
infusion of albumin during and after their
procedure to replete circulating systemic
volume and stabilize vital signs (Smeltzer et al.,
2010).
According
to
the
AASLD,
abdominal
paracentesis should be performed and ascitic
fluid obtained from patients with clinically
499
apparent new-onset ascites (Garcia-Tsao et al.,
2007). These guidelines do not recommend the
routine prophylactic use of fresh frozen plasma
or platelets before paracentesis since bleeding is
sufficiently uncommon. The initial laboratory
studies of ascitic fluid should include a cell
count and differential, total protein, and
serum-ascites albumin gradient (SAAG) as well
as cultures if infection is suspected. Patient
management also includes sodium restriction
and diuretics. Liver transplantation should be
considered in patients with cirrhosis and
ascites.
Additionally,
serial
therapeutic
paracenteses should be considered a treatment
option for those with refractory ascites. For
large-volume paracenteses, an albumin infusion
of 6–8 g/l of fluid can be considered.
Lesser-volume paracenteses may not require
this intervention (Runyon, 2009).
Clinical Pearls—Patient
Management and Treatment
In order to identify life-threatening
hypovolemia practitioners must closely
monitor the ESLD patient after paracentesis.
Vital signs are closely scrutinized at 15 min
intervals until the patient is stable. The
puncture site from the paracentesis should
also be monitored for the presence of
bleeding or hematoma formation. Fluid
500
resuscitation with albumin, blood,
coagulation factors, or other colloids may be
needed for the unstable, hypotensive, or
bleeding patient.
Nutritional assessment and
treatment
The patient with liver disease or other GI
disease requires an extensive nutritional history
and assessment of nutritional parameters. The
nutritional assessment includes an evaluation
of
laboratory
data,
anthropometric
measurements, physical examination, and
pertinent health history (Urden, Stacy, and
Lough, 2010). The nutrition assessment
includes the measurement of acute phase
proteins such as albumin and prealbumin and
evaluates hematologic values to determine
deficiencies (Urden, Stacy, and Lough, 2010).
Evidence-based treatment guidelines
Ensuring adequate protein-calorie nutrition in
all stages of liver disease is a highly
recommended intervention for patients with
liver disease, particularly ESLD (Sundarum and
Shaikh, 2009). Guidelines published by the
European Society for Clinical Nutrition and
Metabolism recommend that patients with
cirrhosis have an energy intake of 35–40 kcal/
501
kg/day and a protein intake of 1.2–1.5 g/kg/
day. If oral intake is inadequate, additional oral
nutritional supplements or tube feeding should
be commenced (Plauth et al., 2006).
Monitoring of patients as they receive these
recommended nutrients includes nutritional
intake history and laboratory assessment as
described earlier.
Critical monitoring in acute
pancreatitis
Many GI illnesses may result in critical illness
and the need for intensive care monitoring.
Those patients who develop severe acute
pancreatitis often require intensive monitoring
and care as they have great potential for
experiencing any one of a number of systemic
and local complications, none the least of which
are hypovolemic shock and infected pancreatic
necrosis. The two most important markers of
severity in acute pancreatitis are organ failure
(particularly multisystem organ failure) and
pancreatic necrosis (Banks and Freeman,
2006).
Patients with severe acute pancreatitis are
monitored closely for the development of
respiratory complications while in the critical
care unit. The onset of hypovolemic shock,
acute lung injury, or sepsis must be identified
rapidly and treated aggressively with volume
resuscitation, intubation and mechanical
502
ventilation, antibiotic therapy and/or surgery.
Additionally, in order to ensure achievement of
the goal of adequate volume resuscitation,
central venous pressures or pulmonary artery
pressures are often monitored in this
population. Most recently, less invasive
monitoring with cardiac output measurement
via pulse contour waveform analysis, which
calculates stroke volume and/or cardiac output
derived from an arterial catheter (as previously
described), has been used for assessment of
volume status.
Evidence-based treatment guidelines for
acute pancreatitis
Published guidelines in acute pancreatitis
include vigorous fluid resuscitation monitored
in a variety of ways including a progressive
decrease in hematocrit at 12 and 24 h post
diagnosis. Bedside oxygen saturation should be
monitored at frequent intervals and blood gases
should be obtained when clinically indicated,
particularly when oxygen saturation is ≤95%.
Patients should be monitored in an ICU if there
is sustained organ failure or there are other
indications that the pancreatitis is severe
including oliguria, persistent tachycardia, and
labored respiration (Banks and Freeman,
2006). However, no guidelines currently exist
for the use of hemodynamic monitoring in the
setting of severe acute pancreatitis.
503
Monitoring elements: pancreatitis
Meeting nutritional needs in acute pancreatitis
is a mainstay of treatment. Based upon many
randomized,
controlled
studies,
experts
recommend the use of enteral feedings, which
are believed to stabilize gut barrier function and
reduce gut permeability to bacteria and
endotoxins. When the goal of optimum
nutritional support is achieved, systemic
complications may be reduced and morbidity
and mortality statistics improved (Banks and
Freeman, 2006).
Evidence-based treatment guidelines for
acute pancreatitis
As with many GI disorders there are practice
guidelines addressing nutrition in patients with
acute pancreatitis. Patients who are unlikely to
resume oral nutrition within 5 days due to
sustained organ failure or other indications
require nutritional support. Whenever possible,
enteral feeding rather than total parenteral
nutrition (TPN) is suggested for patients who
require nutritional support (Banks and
Freeman, 2006).
Patients who are suspected of harboring
gallstones as the mechanism for their
pancreatitis and who have signs of severe
systemic toxicity should undergo endoscopic
retrograde
choangiopancreatography
with
sphincterotomy and stone removal. Regardless
504
of the cause of the acute pancreatitis, patients
should not receive prophylactic antibiotics. It is
reasonable
to
administer
appropriate
antibiotics in necrotizing pancreatitis with signs
of infection and/or organ failure while cultures
are being obtained. Antibiotics should be
discontinued if no source of infection is
identified. In the setting of an expected
infection of necrotic pancreatic parenchyma,
CT-guided percutaneous aspiration with Gram’s
stain and culture is recommended. The
treatment of choice for infected necrosis is
surgical debridement if the patient can tolerate
it. Other less invasive techniques such as
endoscopic and radiologic debridement may be
undertaken in centers that have the capabilities
to perform these procedures (Banks and
Freeman, 2006).
Summary
GI disturbances are a frequent issue in critically
ill patient care. In this chapter, monitoring
modalities and nursing management priorities
have been highlighted. As research advances
clinical understanding of GI management and
treatment, additional standards of practice will
emerge. Currently, overall evidence for
monitoring and surveillance is moderate and
much further research on effective protocols to
enhance patient outcomes is needed.
505
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512
Chapter 10
Traumatic injuries: Special
considerations
Catherine L. Bond and Mary Beth Voights
Carle Foundation Hospital, Urbana, IL., USA
Trauma is the leading cause of death for
persons less than 44 years of age and the fifth
leading cause for all ages (Center for Disease
Control [CDC], 2010). Injury results from a
transfer of energy to the body tissues. The exact
mechanism and patient’s tissue resistance to
that force will determine the exact injuries.
Expected injuries differ based on type and
speed of blunt mechanisms (unrestrained
driver with side impact, pedestrian struck by
motor vehicle, fall from 30 ft landing upright,
diving into 4 foot pool, etc.). Weapon, predicted
path, velocity, and caliber of the missile, along
with distance of the victim from the perpetrator
will provide insight into the expected injuries in
the patient with penetrating trauma. The reader
is directed to more in-depth kinematic
references to further develop their knowledge of
this
concept
if
desired
(McQuillan,
Flynn-Makic, and Whelan, 2008).
513
Primary, secondary, and tertiary
surveys
Standardized, sequential evaluations of the
trauma patient are the best methods to identify
injuries. This evaluation is divided into three
distinct surveys with specific assessments,
interventions, and goals (see Table 10.1). The
American College of Surgeons (ACS) (2008) has
developed the primary and secondary surveys
to rapidly evaluate and correct life-threatening
injury along with a standardized exam to
identify most of the significant injuries.
Table 10.1 Primary and secondary survey of
the trauma patient.
Primary
survey
Life threat/
assessment
Intervention
Airway
Airway
obstruction
Airway maneuvers
Breathing
Mechanical airways
Tension
Needle thoracentesis/
pneumothorax chest tube
Massive
hemothorax
Chest tube/
autotransfusion
Open
Three-sided dressing/
pneumothorax chest tube
Flail chest
514
Pressure support
ventilation
Primary
survey
Life threat/
assessment
Intervention
Circulation
Cardiac
tamponade
Pericardiocentesis
Hypovolemic
shock
Direct pressure to
hemorrhaging wounds/
fluid bolus/targeted
therapy
Expanding
focal
hematoma
Craniotomy/targeted
therapy
Neurogenic
shock
Fluid bolus followed by
pressor agents
Disability
Exposure/back
Missed life
threat wound
Secondary
survey:
head-to-toe
exam
Assessments Interventions to
define/manage
Head
Scalp/skull
injuries
Scalp for
laceration,
hematomas,
evidence of
fracture/
palpable
defects
515
Soft tissue management
(cleansing, repair)
Primary
survey
Life threat/
assessment
Intervention
Head injury
Otorrhea/
rhinorrhea
If open fracture, IV
antibiotics and anticipate
surgical intervention
Eye injury
Level of
consciousness,
GCS, pupils,
and presence
of eye injury
CT scan to define
neuroinjury
Face/dental
Bone/teeth/
nerve or soft
tissue injuries
Ocular shield/prevent
pressure if open globe
Nerve and
CT/panorex scan for
bony integrity; facial/dental fractures
malocclusion
Neck
Deformity,
pain,
tenderness,
Bony, laryngeal, crepitus,
expanding
vascular,
hematoma,
esophageal
bruit
injuries
Maintain spinal
stabilization/collars;
cervical spine CT scan
Laryngoscopy
Angiography/duplex
exam
Esophagoscopy
Chest
Chest wall
tenderness,
crepitus,
decreased
breath sounds
516
Chest X-ray or CT; tube
thoracostomy if hemo/
hemopneumothorax or
pneumothorax visible on
plain film or respiratory
Primary
survey
Life threat/
assessment
Intervention
distress (occult
pneumothoraces do not
require tube
thoracostomy)
Rib, pneumo/
Sub Q
hemothoraces, emphysema
pulmonary
contusion,
tracheobronchial
or vascular/
cardiac injury
Pain management
Unequal arm
BP or pulse
Angiography, contrast CT,
or transesophageal (TE)
echocardiogram
Severe back
pain
Percardiocentesis
Muffled heart
tones
Abdomen/
flank
Distention,
tenderness,
guarding,
rigidity, signs
of bleeding
(Kehr, Cullen,
Gray–Turner)
Intraabdominal
or
retroperitoneal
Open wounds/ CT scan with
potential
contrastExploratory
trajectory
laparotomy
517
Gastric
decompressionUltrasound
or diagnostic Peritoneal
lavage
Primary
survey
Life threat/
assessment
Intervention
Pelvis/
perineum
Hematuria,
perineal
hematomas
Retrograde urethrogram
Genitourinary
injury
Unstable
pelvis/wide
symphysis
Cystogram
Pelvis fractures
Rectal exam
Suprapubic catheter if
for select
ureteral or bladder
patients: tone/ disruption
frank blood/
high riding
prostate
Rectal injury
Vaginal exam
for selected
patients
injury;
abdominal wall
injury
Pelvis X-ray or CT with
contrast
Pelvic stabilization (wrap/
binder/C clamp)
Arterial embolization for
persistent hypotension
without alternate cause
Spine
Pain,
tenderness,
stepoffs
518
Spinal stabilization
(collars/logroll) until
radiologic or clinical
clearance
Primary
survey
Life threat/
assessment
Intervention
Bony or cord
injuries
Motor
function
CT scan or plain X-rays
Nerve root
injury
Sensory
perception
MRI
Extremities
Pain,
tenderness,
deformity,
edema
Immobilization (splint/
surgery)
Fractures
Defects,
lacerations
Targeted X-rays
Joint instability
Pulse deficits, Doppler/angiography/
pallor
interventional
embolization
Soft tissue injury Tense muscle Compartment pressure
compartments measurement/fasciotomy
Vascular injury
Peripheral
Peripheral nerve nerve deficits
injury
Skin/wounds
Lacerations,
hematomas,
deep
abrasions,
burns/
frostbite
Cleansing, repair
Ice packs
The primary survey takes approximately 90
seconds and should be performed with each
519
first patient encounter as life-threatening
conditions can develop as a result of missed
injuries, massive fluid resuscitation, or systemic
inflammatory response syndrome (SIRS). The
secondary survey is a head-to-toe assessment
designed to include each body system, identify
significant injuries, and prompt appropriate
and prioritized intervention. The tertiary survey
is a systems-based assessment including a
review of diagnostic studies and lab results
(Table 10.2). It should be performed each day to
identify covert or evolving injuries or
complications. This survey is an essential
component for advanced practice nurses
(APNs) in the postresuscitation phase of care.
Table 10.2 Tertiary survey of the trauma
patient.
520
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Head
Confirm/rule out
vault fractures
Scalp for
laceration,
hematomas,
evidence of
fracture
Level of
consciousness,
GCS, pupils, eye
movement, and
visual acuity
Review head CT:
results/
recommended
follow-up
Evaluate/
confirm severity
of brain injury
based on clinical
exams and
diagnostic
studies
Confirm/rule out
ocular and
cranial nerve
injury
521
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Potential
consultants:
neurosurgery,
ophthalmology,
plastics
Face
Facial nerves;
bony integrity;
malocclusion;
CSF leak,
hemotympaneum,
hearing loss
Evaluate/rule
out facial and
basilar skull
fractures and
cranial nerve
injury
Potential
consultants: oral
maxillofacial,
ENT, plastics
522
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Neck/
cervical
spine
Soft tissue injury,
swelling,
subcutaneous
emphysema
Evaluate/rule
out neck,
laryngeal,
vascular, and
spine injury or
need for more
detailed
radiologic exams
Spine stepoffs/
pain/tenderness
Potential
consultants:
spine,
gastroenterology,
vascular,
interventional
radiology
Review cervical
spine clearance
(radiographically
or clinically)
523
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Chest
Soft tissue injury,
subcutaneous
emphysema,
tenderness or
deformity,
paradoxical
movement
Pain control;
consideration of
epidural
analgesia or
topical patch
Breath sounds
Chest tube
presence/
function/output
Hemodynamic
values
Need for
ventilatory
support
Review chest
X-ray or CT scan
Need for volume
replacement,
pressor support
or diuresis
Need for
follow-up
detailed
radiologic exams
524
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Note incidental
findings and
implications/
need for future
evaluation
Potential
consultants:
cardiovascular
surgery,
cardiology
525
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Abdomen
Ecchymosis, open
wounds,
tenderness,
guarding, or
masses
Wound care/
need for
antibiotic
therapy
Hemodynamic
values
Evaluate/
confirm
abdominal or
renal injury
Urinary output
Need for
follow-up
detailed
radiologic exams
Tube/drain
outputs
(character and
volume)
Note incidental
findings and
implications/
need for future
evaluation
Review CT scan
Potential
consultants:
urology
526
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Pelvis
Palpate for
stability
Confirm or rule
out pelvis/
acetabular
fractures
Hemodynamic
values
Need for
follow-up
detailed
radiologic exams
Review pelvis CT
scan or X-ray
Note incidental
findings and
implications/
need for future
evaluation
Potential
consultants:
orthopedic,
interventional
radiology
527
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Back
Inspect entire
posterior surface
of head/body for
soft tissue injury
Confirm or rule
out spine injury
Palpate spine and
ribs for
deformity/
stepoffs/
tenderness
Need for
follow-up
detailed
radiologic exams
Review spine
X-rays/CT scan/
MRI
Note incidental
findings and
implications/
need for future
evaluation
Potential
consultants:
spine
528
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Extremity
Confirm or rule
out extremity
injury
Inspect for soft
tissue injury
Assess circulation Identify need for
follow-up
detailed
radiologic exams
Assess motor
function
Note incidental
findings and
implications/
need for future
evaluation
Assess sensory
integrity
Potential
consultants:
orthopedics,
vascular, plastics
Assess joint
integrity
Palpate for
tenderness,
crepitus, edema,
pain with
movement, tense
Review X-rays
529
Tertiary
Assessments
Survey:
head-to-toe
exam and
review of
diagnostic
exams/
plan
Goals
Skin
Local wound
care
Assess for soft
tissue injury
Possible
consultants:
wound care,
plastics
Lab
Review lab results Identify need for
follow-up
detailed exams
Initiate
surveillance labs
Biffl, Harrington, and Cioffi (2003) noted that
this survey is especially important in the
absence of a full secondary survey. Not
surprisingly, their group identified more missed
injuries in patients with higher acuity. The
more critically injured patients often have an
abbreviated secondary survey to accommodate
emergency surgical procedures and altered
neurologic function, which limits the secondary
survey.
Inadequate,
misinterpreted,
or
unordered radiologic exams, admission to a
530
nonsurgical service, and low index of suspicion
add to the potential for missed injury or
unrecognized development of complications
(Hollingsworth-Fridlund, 2001). The surveys
should be performed by each provider caring
for the patient as the multidisciplinary
approach will often reveal the most complete
set of injuries that require intervention.
An additional family survey begins in the
intensive care phase. This survey, completed by
bedside providers, social work, chaplaincy, case
management, and rehabilitation coordinator,
assesses the strengths and options of the family
considering the acuity, impact, and likely
disposition of these patients. For some, the task
of caring for the acutely injured patient is
overwhelming and alternate dispositions
(extended care, nursing home, or hospice) must
be pursued early versus targeting disposition to
rehabilitation or home. Early survey of the
expected physical, psychosocial, and emotional
outcomes of the patient’s injury and factors that
will impact their return to functional status
should guide the treatment plan beginning in
the intensive care unit (ICU) phase of care.
Fluid resuscitation
Controversy exists regarding fluid resuscitation
of the trauma patient. Clear guidelines for
which fluid to use, when to introduce colloids,
531
and when to end measures of resuscitation are
lacking.
Fluid choice
Crystalloids remain the fluid of choice for the
initial replacement of vascular space losses.
Lactated ringers solution remains the preferred
choice (American College of Surgeons
Committee on Trauma, 2008). Recent studies
suggest that lactated ringers could be
deleterious and normal saline is preferred
(Adewale, 2009). Targeted initial volume
replacement is a 1–2 liter bolus for adults and
20 cc/kg for children. Ongoing volume is
calculated to produce adequate urine output
(>0.5 cc/h for adults; 1 cc/kg/h for children,
and 2 cc/kg/h for infants).
Hypertonic saline shows some promise for
hemorrhagic shock replacement with limited
postresuscitation lung injury and the added
benefit of osmotic diuresis for the head injured
population (Adewale, 2009).
Approximately 25% of the crystalloids will be
retained in the vascular space; 75% will
extravasate into the interstitial space (Boldt,
2008). Increased fluid volume will sequester in
the thoracic region and associated electrolyte
imbalances should be anticipated (McQuillan,
Flynn-Makic, and Whelan, 2008).
Blood products are transfused in response to
ongoing hemorrhage. Initial replacement, based
532
on time of availability, will include nontyped or
cross-matched blood (O-negative for women of
childbearing age; O-positive for others),
followed by type-specific and fully
cross-matched blood. Additional components
(fresh frozen plasma, platelets, cryoprecipitate)
are added based on ongoing losses and
laboratory results.
Massive transfusion protocols
Product ratios differ and no single ratio has
been determined to yield the best outcomes at
this point (Shaz et al., 2010). Table 10.3
contains a copy of the shipment table used in
our institution based on current nonmilitary
literature. The shipments of blood product
continue until the active bleeding has been
controlled, injury site oozing becomes limited,
end points normalize (arterial pH, hemoglobin/
hematocrit, fibrinogen, platelets, core
temperature), or efforts are recognized as futile.
Table 10.3 Massive transfusion product (MTP)
shipment table.
Labs
Shipment RBC
Original 1
panel
with MTP
protocol
activation
6
(O-negative)
or
O-positive if
male >16
years
533
FFP Platelets CRYO
4
1
(AB)
sent
as
soon
as
ready
Labs
Shipment RBC
FFP Platelets CRYO
2
6
4
Coags
3
collected
6
4
4
6
4
Coags
5
collected
6
4
6
6
4
Coags
7
collected
6
4
8
6
4
Coags
9
collected
6
4
1
1 if
platelet
count
<50 K
10 if
fibrinoge
<100 mg
dl
1 if
platelet
count
<50 K
10 if
fibrinoge
<100 mg
dl
1 if
platelet
count
<50 K
10 if
fibrinoge
<100 mg
dl
Clinical Pearls
The key is to have these protocols in place
before they are needed. Their development
534
and ongoing success are a collaborative effort
of the surgeons, anesthesiologists,
intensivists, blood bank, phlebotomy, and
nursing.
End points of resuscitation
An extensive review of the literature was
undertaken by Tisherman and colleagues
(2004) to define optimal end point
measurements for trauma resuscitation. Their
work has become a guideline in the Eastern
Association of Surgery for Trauma (EAST).
Tisherman et al. (2004) noted that standard
clinical parameters (blood pressure, heart rate,
urine volume) are inadequate markers of organ
perfusion. Multiple other measurements
including hemodynamic profiles, acid–base
status, gastric tonometry, and regional
measures of tissue O2 and CO2 levels have been
used and studied to determine which, if any, are
preferred. This review could not identify a
specific parameter that was optimal in
monitoring patients to prevent organ failure
and death, resulting in a recommendation to
utilize any one of these more discrete
measurements rather than the standard vital
signs and urinary output to measure
effectiveness of resuscitation efforts. No studies
since the deployment of this guideline have
refuted this recommendation. An entire Critical
535
Care Nursing Clinics volume was devoted to
ongoing monitoring and hemodynamics and
includes more details on each of these
modalities (Leeper, 2006). Articles within this
edition that are most useful when addressing
patients with traumatic injury include
transcutaneous CO2 Monitoring; End Tidal CO2
Monitoring; Bispectral Index Monitoring
during Sedation; and Brain Tissue Oxygen
Monitoring.
Intracompartmental monitoring
The brain lives in a closed space with finite
limits and little room for anything extra. In an
adult, the intracranial volume is 1200–1500 cc.
The three components of cerebral volume are
cerebral tissue (80%), cerebral blood flow
(12%), and cerebrospinal fluid (8%). Any
increase in volume in one compartment must
be matched by a similar reduction in another
compartment or intracranial pressure (ICP) will
rise. This is known as the Monroe–Kellie
hypothesis. The objective of ICP monitoring is
to optimize cerebral perfusion pressure (CPP)
and oxygenation and minimize secondary brain
injury while allowing time for the brain to heal.
CPP is an indirect reflection of cerebral
perfusion: mean arterial pressure (MAP) minus
ICP. CPP less than 50 is associated with poor
outcomes. Continuous monitoring of ICP and
blood pressure is the key to managing the
changes in the three components of cerebral
536
volume that shift and can cause cerebral
hypoperfusion and ultimately herniation (A
Joint Project of the Brain Trauma Foundation
and American Association of Neurological
Surgeons, 2007). These guidelines support ICP
monitoring of patients with severe traumatic
brain injury and a normal head computed
tomography (CT) and who have any two of the
following present on admission: age over 40
years, unilateral or bilateral motor posturing, or
systolic blood pressure less than 90. Monitoring
of ICP in patients with a Glascow Coma Score of
8 or less with an abnormal CT scan is a
supported recommendation from the Brain
Trauma Foundation (2007) Guidelines for the
Management of Head Injury. Data from
monitoring ICP can be used for prognosis,
guiding therapies aimed at reducing ICP,
increasing
MAP,
measurement
of
intraventricular pressure, and guidance of
therapeutic drainage of cerebrospinal fluid to
decrease cerebral volume. Increasing ICP can
be one of the first signs of worsening brain
edema or bleeding that may require surgical
intervention. See also Chapter 6.
Figure 10.1 using concepts further detailed in
Bullock et al. (2006), Coplin, 2001, Cushman et
al. (2010)., and Schirmer et al. (2008),
illustrates the relationship of elements used in
managing head injury patients.
537
Figure
10.1
Traumatic
brain
injury
management algorithm, Carle Foundation
Hospital.
*Unless ICP rises >20.
**Stop if PbtO2 falls <20.
***Vasopressors to bring CPP > 60. Inotropes
to increase CI.
****If CPP < 60, consider inotropes. If CPP <
60, consider vasopressors.
NOTE: This protocol provides for all factors
that should be considered.
538
Complications
Caring for trauma patients is not just about
knowing how to deal with the injuries, but
being able to anticipate and prevent
complications. Patients are at risk for some
complications simply due to pain and
immobility. Other complications are more
specific to the mechanism or injury itself. Many
times the risks revolve around some alteration
in clotting. Many patients are at risk for deep
vein thrombosis (DVT) or emboli from areas of
vascular injury. Other patients may have
prolonged clotting, such as patients who are on
chronic anticoagulation or who develop
disseminated intravascular coagulation (DIC).
Thromboembolic events
Just as in any bedridden patient, DVT is always
a risk. One of the issues in trauma is whether
DVT prophylaxis is safe for the patient. Patients
with intracranial bleeding, solid organ injury, or
major pelvic fractures are at high risk of
bleeding, and therefore may need to go without
any anticoagulants for 72 h or more. While
low–molecular
weight
heparin
or
unfractionated heparin may increase risk of
expansion of intracranial hemorrhages, Dudley
et al. (2010) showed that patients with two
consecutive
CT
scans
demonstrating
hemorrhagic stability who were started on DVT
prophylaxis within 48–72 h had relatively high
539
protection from thromboembolic events and
low risk of intracranial hemorrhage. Inferior
vena cava (IVC) filters can be used for patients
at high risk of DVT who cannot be
anticoagulated for many days but IVC filters are
not without risk. Other patients can have
potential for upper extremity clots either from
antecubital peripherally inserted central
catheter (PICC) lines or upper extremity
vascular injury. Superior vena cava (SVC) filters
are difficult to place and come with their own
set of potential complications. Patient data
from the Trauma Registry of the German
Society for Trauma Surgery, including 35,000
trauma patients screened for clinically relevant
venous thromboembolic events (VTEs), found
that 80.8% of patients with VTE were under
chemical or mechanical prophylaxis at the time
of the event, and two-thirds of the events
occurred within 3 weeks of admission (Paffrath
et al., 2010).
Clinical Pearls
Devastating injury from carotid or vertebral
artery dissection or flaps causing emboli to
travel to the brain resulting in stroke may
also arise. Recently, in our trauma center, a
21-year-old patient suffered right-side
hemiparesis and expressive aphasia from a
clot to the middle cerebral artery following
540
cervical hyperextension in a motor vehicle
crash.
Anticoagulation
Many older patients are admitted with some
type of anticoagulation. Warfarin and various
platelet inhibitors can cause bleeding problems
after trauma. Older patients with falls are often
admitted with intracranial bleeding related to
chronic anticoagulation or antiplatelet drugs.
Bleeding risk in solid organ injury or major
orthopedic injury also increases with elevated
international normalized ratio (INR) or
decreased
platelet
function.
Massive
transfusion protocols may be utilized for
anticoagulated patients who require emergent
surgery and develop DIC (see Table 10.3). Older
patients requiring reversal of anticoagulation
may require multiple units of fresh frozen
plasma and require close monitoring for fluid
overload.
Pain management
Many complications are directly related to pain
control. In trauma patients, pain control is
extremely important to avoid complications
associated
with
immobility
and
hypoventilation. Patients with chest trauma,
including multiple rib fractures and pulmonary
contusions, need adequate pain control in order
541
to continue with aggressive pulmonary toilet to
prevent pneumonia and lobar collapse.
Pneumonia may develop secondary to a
combination
of
factors
including
hypoventilation, aspiration, inadequate pain
management, atelectasis, and pooling of
secretions.
Early mobilization
Mobilization is also a key factor in the
prevention of complications. While historically
the ICU has not been a place where patients
spend a lot of time out of bed, new studies
support
mobilizing
even
mechanically
ventilated patients (Bourdin, 2010; Kress,
2009). This requires a multidisciplinary team
effort including nurses, respiratory, physical,
and occupational therapies. The improvement
in outcomes such as ability of patients to
ambulate on discharge and shortened length of
stay make the coordination of these
interventions essential and worth the effort
(Kress, 2009). Bourdin (2010) found that
getting the ICU patient into the chair resulted
in a decline in heart rate by a mean of 3.5 beats
per minute and decreased respiratory rate of 1.4
breaths per minute, while oxygen saturation
and arterial blood pressure were not adversely
affected. While there can be many barriers to
getting trauma patients out of bed, the positive
outcomes include improvement in pulmonary
status, gut function, and overall endurance.
542
Thoracic injury management
Rib fractures can easily be underestimated as a
major injury. Patients, especially elderly
patients, can very quickly decompensate as they
take only very shallow inspirations due to pain
from multiple rib fractures. The gold standard
for pain control in rib fractures is the use of the
epidural infusion for analgesia (Simon et al.,
2012). However, this can only be used in
patients without exposure to anticoagulation
and without spinal injury. When an epidural is
not possible, scheduled oral medication or
patient-controlled analgesia combined with a
continuous infusion of narcotic may be
warranted. Patients must be carefully
monitored for respiratory depression. The
balance between adequate pain relief and
neurologic and respiratory depression is a key
measure for continuous monitoring.
Another risk associated with chest injury is
pleural effusion. The patient with rib fractures
and/or pulmonary contusion is at risk for
effusion 3–5 days post injury. Patients already
at risk for respiratory insufficiency may have
worsening inspiratory volumes due to the
collection of pleural fluid, limiting tidal volume.
Drainage with chest tubes or thoracentesis is
often required. These patients are followed
closely with daily chest X-rays and continuous
oxygen saturation monitoring.
543
Use of narcotics for pain control can contribute
to respiratory depression and increasing carbon
dioxide levels, not readily apparent in oxygen
saturation monitoring. These patients may
require alternate modes of both oxygen delivery
and ventilation support. Use of bilevel positive
airway pressure (BiPAP) for ventilation support
or continuous positive airway pressure (CPAP)
for oxygenation support may become necessary
to prevent progression to respiratory failure
(see Chapter 3).
Pneumothorax or hemopneumothorax may
occur as the primary injury in blunt chest
trauma, or can occur as a possible complication
from rib fractures or pulmonary contusion.
Chest tube thoracotomy is the treatment of
choice. Pain control is again important for these
patients and monitoring for adequate
oxygenation and ventilation is essential. Not
only are rib fractures painful, but the insertion
of the chest tube adds to the painful experience.
Empyema may develop due to inadequately
drained hemothorax, infected parapneumonic
effusion, trauma, esophageal perforation, or
bronchopleural fistula (Ahmed & Zangan,
2012).
Abdominal trauma
Abdominal trauma can be classified as blunt or
penetrating. Complications may include
bleeding and infection. Bleeding can occur from
544
inadequate hemostasis or coagulopathy.
Hypothermia from administration of multiple
blood products, large volumes of room
temperature fluids, or prolonged operating
room time can also cause coagulopathy. Other
complications include intra-abdominal abscess,
cholangitis, and biliary fistula. Splenic injuries
may result in complications, with the most
serious overwhelming post-splenectomy sepsis
(OPSS) occurring in 1–2% of patients. OPSS is
characterized by an initial “flu-like” syndrome
followed by an abrupt onset of fever, chills,
nausea, and vomiting. Post-splenectomy
patients are prophylactically immunized with
pneumococcal (Pneumovax), meningococcal,
and Haemophilus influenzae vaccines to
prevent this. Initial treatment is focused on
trying to preserve the spleen, but if watchful
waiting is unsuccessful, post-op complications
can include bleeding, abscess formation, and
pancreatitis.
All trauma patients are at risk for bowel
complications. Specific injuries may cause
patients to be at higher risk for paralytic ileus.
In penetrating trauma, small bowel injury is the
most commonly seen (up to 80%) in gun shot
wounds (GSWs) and also has a high incidence
in general penetrating trauma. Common
complications include hemorrhage, suture line
disruption, and small bowel malabsorption
syndrome. Pelvic fractures, thoracic and lumbar
spine injuries, repetitive anesthesia, and
545
abdominal organ injury cause decreased bowel
motility and, combined with narcotics for
analgesia and immobility, can result in
prolonged hospital stays, delay to enteral
nutrition, and discomfort to patients (Johnson
& Walsh, 2009). See Table 10.4 for differential
diagnoses, diagnostic exams, and management
strategies.
Table 10.4 Differential diagnosis and
management of gastroparesis, small bowel
ileus, and colonic ileus.
Adapted
from
http://www.uptodate.com/
contents/
etiology-and-diagnosis-of-delayed-gastric-emptying
Condition
Symptoms Signs
Gastroparesis Nausea +++ Distention
Vomiting
Succussion splash
+++
Abdominal
pain +
546
Precipitat
factors
Diabetes
Vagal nerve
(gastric/tho
surgery)
Viral
Ideopathic
Connective
diseases
Narcotics
Alpha-2-ad
agonists (e.
clonidine)
Tricyclic
antidepress
Condition
Symptoms Signs
Precipitat
factors
Calcium cha
blockers
Dopamine a
Muscarinic
cholinergic
antagonists
Octreotide
Exenatide a
glucagon-lik
(GLP)-1 ago
Phenothiaz
Neurologic
Autoimmun
disorders
Psychiatric
Small bowel
ileus
Nausea
Bowel sounds:
++Vomiting high-pitched or
++
absent Distention
No peritoneal signs
Abdominal
procedures
Abdominal
inflammatio
(appendicit
abscess/cho
pancreatitis
abdominal
retroperiton
hemorrhage
Anticholine
Abdominal Dilated loops of
pain
bowel, paucity of
+“Gasiness”
Antihistami
OpiatesHyp
547
Condition
Symptoms Signs
Precipitat
factors
colonic gasLittle or hypomagne
no flatus
SepsisUrem
Colonic ileus
Nausea
+Vomiting
+Abdominal
pain +
Bowel sounds:
quiet or
absentDistentionNo
peritoneal signs
Dilated loops of
bowel, paucity of
colonic gasNo flatus
All patients can benefit from a bowel protocol
and timely nutrition. Nutrition can be delayed
for days due to a dysfunctional gastrointestinal
system. This may necessitate the use of total
parenteral nutrition (TPN). Early enteral
nutrition (within the first 24 h) is associated
with earlier return of bowel function. To
encourage bowel function, stool softeners and
laxatives with promotility agents are often
548
Abdominal
procedures
Abdominal
inflammatio
(appendicit
abscess/cho
pancreatitis
abdominal
retroperiton
hemorrhage
Anticholine
Antihistami
Opiates
Hypokalem
hypomagne
Sepsis
Traumatic i
Uremia
added as necessary. A combination of daily
laxatives such as milk of magnesia, miralax, and
senna/docusate combination is generally
effective. In patients with pelvic fractures,
thoracic or lumbar spine fractures, or those
with
abdominal
injuries,
intravenous
metacloprimide (reglan) every 6 h is commonly
used and erythromycin may be added
intravenously. Constipation is increased by
narcotic use and decreased immobility. Close
monitoring of patients’ bowel movements is
essential. This can easily be missed in the face
of many other issues in the complex trauma
patient. In one study, constipation occurred in
69.9% of ICU patients (Nassar, Queiroz da
Silva, and De Cleva, 2009).
Abdominal compartment syndrome
The vital organs of the body are contained
within compartments, surrounded by thick
walls of fascia, connective tissue, or bone.
Increased pressure within a compartment
causes decreased blood flow and dysfunction of
the organs or tissues contained within. See
Table 10.5 for signs and symptoms. Increased
pressure in one compartment not only affects
the organs within that space, but can cause
increased pressure and organ dysfunction in the
other compartments of the body.
Table 10.5 Organ dysfunction caused by
increased intracompartmental pressure.
549
Adapted from Balogh and Butcher (2010).
Organ/
Signs and/or symptoms
body part
or system
Brain
↑ intracranial pressure
Lungs/
↑ airway pressures, ↓ pulmonary
respiratory compliance (stiff lungs),
hypoxemia, CO2 retention
Chest/
heart/
circulation
↑ chamber filling pressures, ↓
cardiac output, ↑ systemic
vascular resistance
Gut/
intestine
↓ intestinal pH, intolerance of
enteral nutrition (↑ residual
volumes), bowel edema, ileus,
compromised intestinal barrier
function
Kidneys/
renal
↓ urinary output, ↓ glomerular
filtration rate
Lower
extremities/
venous
system
Venous congestion, edema, ↑
deep vein thrombosis risk,
extremity compartment
syndromes
Abdominal hypertension can cause increased
ICP, increased pulmonary pressures causing
decreased compliance, as well as bowel
ischemia, renal failure, and venous congestion,
which can increase risk for DVT and extremity
compartment syndromes (Balogh and Butcher,
550
2010). See Chapter 9 for details of measuring
abdominal compartment pressures.
Trauma surgeons have been performing
damage control surgery for years. The principle
of controlling hemorrhage and keeping the
operating time short, leaving the abdominal
cavity open to prevent compartment syndrome
and facilitate staged procedures has evolved
over many years. Open abdominal wounds used
to be temporarily closed with towels, Bogota
bags, or large wet to dry dressings.
Vacuum-assisted wound closure systems have
become the standard closure for complex
wound management in most trauma centers. By
using negative pressure on the wound bed, fluid
is removed from the extravascular space, which
improves blood supply during the inflammatory
phase of healing. Granulation is promoted in
the wound bed and dressing changes are
generally less painful for patients (Webb,
2002). The time line for the healing process can
involve multiple returns to the operating room
every 2–3 days for assessment of possible
abdominal wound closure. If closure is not
possible, then the abdomen may be allowed to
granulate followed by a skin graft to close the
defect. This process can take 10–14 days. In
addition, the patient may have to wait 6–12
months
for
possible
abdominal
wall
reconstruction to treat ventral hernias (Waibel
and Rotondo, 2010). See Figure 10.2 for
staging.
551
Figure 10.2 Stages of damage control surgery.
Musculoskeletal injuries and
management
Musculoskeletal injury is common in the
trauma population. While pelvic trauma is the
most clinically challenging orthopedic injury to
manage, other orthopedic injuries may cause
significant lifelong morbidity if they go
unrecognized and untreated. The tertiary
552
survey, discussed earlier in this chapter,
remains the best offense in injury identification
and should be utilized to prevent missed injury.
Assessment for musculoskeletal injury includes
inspection for deformity, wounds, ecchymosis,
swelling, position abnormality, extremity color;
palpation for crepitus, tenderness, discontinuity
to palpation of posterior spinous processes,
muscle spasm, peripheral pulses; capillary refill
time; and motor and sensory assessment.
General management strategies for orthopedic
injuries include temporary stabilization to
prevent blood loss, pain, and nerve damage,
followed by long-term stabilization. Timing of
operative fixation remains controversial. The
current recommendations from EAST favor
long bone stabilization within 48 h of injury in
polytrauma patients (Dunham et al., 2001).
Pelvis stabilization timing is dependent on
stability and associated hemorrhage. Early
percutaneous fixation provides a minimally
invasive option to control hemorrhage and
allows for bony stability (Smith and Scalea,
2006). Ongoing monitoring utilizes serial
assessments to prevent and identify any
complications, including infection, concomitant
nerve injury, compartment syndrome, fat
embolism syndrome, deep vein thrombosis, and
ongoing hemorrhage. Preventing infection is
paramount given the complications of
osteomyelitis and nonunion that are associated
with infected bone. Table 10.6 contains the
553
EAST recommendations for prophylaxis and
management of open fractures (Hoff et al.,
2011).
Table 10.6 Prophylactic antibiotic use in open
fractures.
Adapted from Hoff et al. (2011).
Evidence Recommendation
Level I
Systemic antibiotic coverage
directed at gram-positive
organisms should be initiated as
soon as possible following injury
Additional gram-negative coverage
should be added for grade III
fractures
High-dose penicillin should be
added in the presence of fecal or
potential clostridial contamination
(e.g., farm-related injuries)
Fluoroquinolones offer no
advantage compared with
cephalosporin/aminoglycoside
regimens and may have a
detrimental effect on fracture
healing
554
Evidence Recommendation
Level II
Antibiotics should be discontinued
24 h after wound closure for grade
I and II fractures
In grade III fractures, antibiotics
should be continued for 72 h
following injury or not more than
24 h after soft tissue coverage has
been achieved
Single-dose aminoglycoside dosing
is safe and effective for grade II
and III fractures
Concomitant nerve injury is suspected based on
injury location and mechanism. Deficits are
challenging to identify in the ICU patient who is
sedated or has a limited neurologic exam. Serial
evaluation of nerve functionality is critical to
the surveillance of trauma patients. Table 10.7
demonstrates the best strategy for recognizing
deficits.
Table 10.7 Extremity nerve assessment.
555
Nerve assessments
Nerve
Function Examination
Radial
Sensation Pinprick and two-point
discrimination (separate
two ends of a paper clip
by 5 mm) over the dorsal
surface of the thumb web
space)
Motion
Ulnar
Extend the wrist and the
MP joint
Sensation Pinprick and two-point
discrimination over the
distal fat pad of the little
finger
Motion
Compare the strength of
the fingers as the patient
spreads them to the side.
Flex the distal joint of the
little and ring fingers
against resistance.
Adduct the thumb
Median Sensation Pinprick and two-point
discrimination over the
index, middle, and ring
fingers. Coin
discrimination
Motion
Flex the wrist and PIP
joints of the thumb and
index finger against
resistance
556
Nerve assessments
Nerve
Function Examination
Axillary Motion
Abduction of the upper
arm at the shoulder
Femoral Sensation Pinprick discrimination
over the median and
anterior surface of the
thigh and knee
Motion
Tibial
Extension of the leg at
the knee
Sensation Pinprick discrimination
over the medial and
lateral surfaces of the
sole of the foot
Motion
Plantar flexion of the foot
Peroneal Sensation Pinprick discrimination
over the lateral surface of
the great toe and medial
surface of the second toe
Motion
Dorsiflexion of the foot
Compartment syndrome should be suspected
with crush injury or significant fracture and is
most commonly found in the muscles of the
forearm, hand, lower leg, and foot. Fascia is a
tough, fibrous sheath that surrounds the
skeletal muscle, vessels, and soft tissue.
Excessive pressure in the fascial-limiting
compartment restricts perfusion to the muscle
and neurovascular bundle, which results in
557
tissue ischemia, rebound edema, and tissue
necrosis. The presence of open fracture does
not
preclude
compartment
syndrome
development (McQuillan, Flynn-Makic, &
Whelan, 2008). Early signs of this
complication, which may be limited in the
sedated or neurologically compromised patient,
are localized pain out of proportion to the
injury and pain with passive stretch of the
muscles. Diminished pulses, paresthesia, and
paralysis are late signs. Assessing tenseness of
the compartment and use of intermittent or
continuous
compartment
pressure
measurement devices may be needed to
diagnose this complication in the ICU setting.
Compartment pressure can be measured by
using the Stryker Intracompartmental Pressure
Monitor® (Stryker Corporation, Kalamazoo,
Michigan, 2009) or similar devices. Normal
compartment pressures range from 0 to 15
mmHg. Tissue pressures greater than 35–45
mmHg suggest impaired capillary blood flow,
produce clinically significant muscle ischemia,
and may indicate the need for fasciotomy
(American College of Surgeons Committee on
Trauma, 2008). Standard laboratory indicators
of muscle injury are CK, CPK, LDH, AST/ALT,
and urine myoglobin. Patients with multiple
trauma may have many sources of tissue injury,
making elevations of these labs less reliable in
pinpointing compartment syndrome.
558
Ongoing hemorrhage
Ongoing hemorrhage may not be apparent until
the patient is resuscitated and peripheral
vasoconstriction eases. Expanding hematomas
(or those with blush on contrast CT),
diminished distal pulses, unanticipated edema,
hemodynamic
instability
despite
pelvic
stabilization, and dropping hemoglobin/
hematocrit values are all possible signs. Each
long bone fracture generally results in the loss
of several units of blood; bleeding in excess of
that should be investigated (Smith & Scalea,
2006). Angiography is the diagnostic tool of
choice. Level I/II recommendations are (i)
major pelvis fracture with signs of ongoing
bleeding after nonpelvic sources are ruled out;
(ii) major pelvis fracture whose bleeding at the
time of laparotomy cannot be controlled; (iii)
evidence
of
arterial
extravasation
of
intravenous contrast in the CT imaging of the
pelvis; or (iv) patients > 60 years of age with
significant pelvis fractures regardless of
hemodynmaic stability (Cullinane et al., 2011,
p. 1862). Definitive intervention may include
transcatheter embolization, direct ligation, or
bypass grafting.
Pelvic fractures
Pelvic fractures present a unique set of issues
for trauma patients. Due to the forces involved
and location of organs adjacent to the pelvis,
559
major fractures are often accompanied by
genitourinary organ damage or vascular injury
and bleeding. Major pelvic injuries include
traumatic fractures and involving innominate
and sacral bones, joints, ligaments and major
vascular support and due to the valveness
nature of veins in the pelvis, considerable blood
loss can occur even without arterial
involvement (Rajab, Weaver, & Havens, 2013).
Bleeding is one of the more serious
complications seen in pelvic fractures.
Retroperitoneal bleeding is mainly venous; 80%
of the blood loss requiring transfusion in pelvic
fracture is from the fracture site. Pelvic
stabilization with sheet wraps or pelvic binders
can help tamponade bleeding sites. Bladder and
urethral injury is assumed until proven
otherwise. Vaginal or bowel injury, fat emboli,
other bone fractures and soft tissue injury, and
sepsis from infection in open fractures put
patients at risk after major pelvic fractures and
require continuous monitoring and surveillance
by the team.
Crush syndrome management
Crush syndrome is a complication seen in blunt
trauma associated with orthopedic injuries.
Compression of tissues either with extreme
force or for prolonged periods of time often
causes release of toxins that can cause systemic
consequences. Release of pressure and
reperfusion of the area may result in lactic acid,
560
potassium, myoglobin, and uric acid uptake in
the systemic circulation in quantities not
normally found in the bloodstream. Muscle
ischemia followed by reperfusion is the
fundamental pathophysiologic mechanism of
rhabdomyolysis (Malinoski, Slater, & Mullins,
2004). Myoglobin is released, and this large
protein molecule is unable to be filtered by the
kidney, and renal failure can result. Dark,
tea-colored urine that is dipstick-positive for
blood despite the absence of red blood cells
(RBCs) on microscopy is suggestive of
myoglobinuria and rhabdomyolysis (Malinoski,
et al., 2004). Management strategies are
targeted at dilution and avoidance of cellular
toxicity. Large volumes of crystalloid temper
the intravascular deficits caused by fluid
initially sequestered in the injured muscle and
the hyperkalemia of cellular rupture. Sodium
bicarbonate may be added to the intravenous
fluids to increase myoglobin solubility, decrease
renal cast formation, and force alkaline urine
excretion. Mannitol may also be added for its
volume expansion and oxygen-free radical
scavenger properties. Studies are conflicting
regarding the true efficacy of these additives
and certainly both have risks. IV fluid delivery
at a rate that yields urinary outputs of 200–300
ml/h for adults is suggested for the first 24 h to
flush the kidneys of myoglobin (Vanholder,
2011). Ongoing monitoring for fluid overload
and hyperkalemia and the cardiac effects is
essential. Hypocalcemia is not corrected unless
561
there is significant symptomatology as the
majority of infused calcium will be deposited
into the injured muscle tissues leading to severe
rebound hypercalcemia as it is released
approximately 24 h post injury (Malinoski,
Slater, and Mullins, 2004; Vanholder, 2011).
Pain management in orthopedic injury
Pain control is also essential for patients with
orthopedic injuries in order to promote
mobility as part of an attempt to prevent
complications from bedrest. Bone fractures are
painful, and pain control can often best be
achieved with nonsteroidal anti-inflammatory
drugs (NSAIDs) such as ketorolac (Toradol).
But due to anticoagulant properties of this drug
class and the risk for hindering bone healing,
many patients cannot tolerate this agent for
pain control. Narcotics are most frequently
used for pain control in this group of injuries.
Burns
Significant burns are generally managed at
burn centers; however, trauma priorities may
require that some burn injuries will need
management at a nonburn center and a brief
summary of management and monitoring
principles follows.
562
Burn classification
Burns can result from various mechanisms:
thermal, electrical, chemical, radiation, and
inhalation. Thermal burn mechanisms are well
known. Electrical/lightning burns will have
tissue damage along the path of current from
entrance to exit. Current follows the path of
least resistance, with blood vessels, muscles,
and nerves sustaining more damage than the
external appearance might suggest. Fractures
secondary to the muscle contractions may be
missed in the intial evaluation. Chemical burns
require copious irrigation/decontamination.
Alkali agents will cause ongoing damage even
after removal of the actual substance.
Inhalation injuries result from a combination of
superheated and toxic gases. Among the foci of
care for the burn population are: fluid
replacement/management, ventilation, local
and end organ cellular perfusion, tissue
coverage, and preventing infection.
Depth of burn is an important assessment.
Partial thickness burns include the epidermis
and upper level of the dermis. Those elements
of the dermis needed for reepithelialization and
nerve endings remain intact. The partial
thickness wound will appear wet, is painful, and
blanches to pressure. Full thickness burns cause
destruction of cell reproduction and will require
a skin graft for coverage. The full thickness
burn will appear dry, leathery, and is insensate.
563
Total body surface area (TBSA) is used as the
measure of tissue involvement. The Rule of
Nines or the Lund–Browder chart for infants
gives a general measure of TBSA (see Figure
10.3). In the absence of a chart, the patient’s
palm can be used to approximate 1% TBSA.
564
565
Figure 10.3 Burn evaluation and Lund/
Browder chart.
From Wiegard (2011). © Elsevier.
Fluid management in burn therapy
Fluid management is guided by several
formulas and guidelines. Direct and indirect
losses will cause a fluid shift from the vascular
space. This begins shortly after the burn, peaks
in 6–8 h and can last up to 48 h (Pham &
Gibran, 2007). Once approximated, the TBSA is
utilized in the following resuscitation formula:
Parkland formula: 2–4 cc lactated Ringer’s
solution/kg/% TBSA partial or full thickness
burns. One half of this volume is infused over
the first 8 h post burn. The other half is infused
over the next 16 h. This is an approximate
volume and should be titrated to urinary
output, which remains the best outcome
measure for these patients (0.5 cc/kg/h for
adults; 1 cc/kg/h for pediatrics).
Pediatric patients will need supplemental
isotonic fluids with dextrose due to their low
glycogen stores (Pham and Gibran, 2007).
Ventilation support will often be required via
mechanical ventilation or pressure support and
hyperbaric oxygen is used in some settings
(Pham and Gibran, 2007). Many centers adopt
low-volume, low–airway pressure ventilation as
their standard and then move to oscillator
566
mode if ineffective (Pham & Gibran, 2007).
Monitoring will include workup of breathing,
arterial blood gases, SpO2, carboxyhemoglobin
levels, and outcome measures of resuscitation
mentioned in the foregoing section.
Cellular perfusion is maximized by volume
replacement and by limiting peripheral
constriction. Serial monitoring should include
distal nerve/motor function and pulse quality.
Compartment
syndrome,
caused
by
circumferential eschar, may limit perfusion and
require escharotomy to release the constriction
and reestablish distal flow. Airway pressures
should drop with chest escharotomy and distal
circulation, motor and sensory function return
with extremity procedures.
Injured muscle may lead to myoglobin and
potassium release, causing obstruction of the
renal tubules with resultant rhabdomyolysis or
cardiac
dysrhythmias,
respectively.
Myoglobinuria
is
identified
by
direct
measurement or port-wine urine that has no
RBCs on analysis. Urinary output goals increase
to 100 ml/h until the urine clears and an
osmotic diuretic may be added to limit
intrarenal failure (Miller, 2009; Pham and
Gibran, 2007). Early surgical debridement of
necrotic muscle may be needed if the
myoglobinuria and acidosis does not resolve
with aggressive resuscitation measures.
567
Pain management is essential. Dressing
changes are painful. Patients who have daily
dressing changes may tolerate pain with
NSAIDs, acetaminophen, and limb elevation.
Patients who require multiple daily dressing
changes and therapy sessions will generally
require narcotics and anxiolytics. Positioning to
limit edema is especially important for both
pain control and tissue perfusion (Miller,
2009).
Aseptic wound care is critical to avoiding
infection and promoting tissue coverage.
Employ personal barrier precautions and
asepsis until all burns are cleansed and covered
with dry sterile dressings and/or clean, dry
sheets. Use a mild soap and water for cleaning.
Avoid substances such as povidone-iodine
solution or chlorhexidine gluconate solution as
they may hamper the healing process. Leave
blisters intact and only debride loose tissue.
Practitioners may aspirate large blisters or
those over a major joint, leaving the roof intact
(Miller, 2009).
A variety of topical antibiotics exist that
penetrate eschar and limit underlying tissue
necrosis. Those most commonly used are silveror sulfa-based. Bacitracin is recommended for
the face. Do not apply cream directly to wound.
Recommended procedure is to “butter” the
dressing with the topical cream and apply the
dressing to the wound. This provides the
568
correct amount of cream (not too thick) and is
far less painful to the patient. Dressing removal
will also provide mechanical debridement
instead of having to scrape the cream off of the
skin. Primary excision and grafting are
standard management for full thickness burns
(Miller, 2009; Pham & Gibran, 2007). Removal
of eschar within 2–4 days of the initial burn
followed by graft placement results in less
overall sepsis and improved adherence of
grafts. Anemia is common secondary to
dilution, surgical debridement, bone marrow
suppression, and frequent lab draws. Red cell
replacement is dependent on hemoglobin level,
patient tolerance, and risk factors.
Summary
In this chapter, evidence-based guidelines
supporting specific injury identification and
management have been reviewed. Clinical
pearls of wisdom gleaned from years of
hands-on experience with trauma patients
where “refereed evidence” does not exist were
also offered. Monitoring the trauma patient can
involve exponential amounts of technology and
complexity. The data obtained can be extremely
valuable but can also distract the APN and
trauma practitioners from the essential
elements of physiologic monitoring principles
embedded in clinical practice. Basic monitoring
including volume status, heart rate, clinical
neurologic exam, fever, pain perception, elicited
569
tenderness, and a high index of suspicion are
the key elements to monitor progress or relapse
of the trauma patient and should not be ignored
in favor of complex technology, but rather
augment it. Nothing can replace a direct,
hands-on assessment of the patient.
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Balogh, Z.J. and Butcher, N.E. (2010)
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Boldt, J. (2008) Fluid choices for resuscitation
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Dudley, R.R., Aziz, I., Bonnici, A. et al. (2010).
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575
Chapter 11
Oncologic emergencies in
critical care
Lisa M. Barbarotta
Smilow Cancer Hospital at Yale-New Haven,
New Haven, CT., USA
Evolution of oncology critical
management
Cancer is the second leading cause of death in
the United States and a leading cause of death
worldwide (Kochanek et al., 2011). Enhanced
critical
care
capabilities,
sophisticated
technology, new oncology treatment strategies,
and earlier detection of complications have
contributed to improved survival of cancer
patients. Survival rates for critically ill cancer
patients have improved dramatically with a
20% decrease in overall mortality between the
years 1978 and 1998 (Thiery et al., 2005).
Improvements in survival may also be
attributed to better selection of oncology
patients appropriate for intensive care settings.
Investigators have tried to define objective
criteria for critical care admission (Groeger and
Aurora, 2001). These criteria include
postoperative care, management of medical
576
emergencies related to cancer or its treatment,
and monitoring during intensive cancer
treatments. Other considerations for intensive
care unit (ICU) admission should include the
likelihood of survival and the patient’s goals
(Shelton, 2010). Performance status and the
presence and number of comorbidities may also
impact survival (Soares and Salluh, 2010).
While factors impacting survival have been
identified, the decision to admit an oncology
patient to the ICU setting must be
individualized.
The
need
for
and
appropriateness of critical care should be
reevaluated regularly throughout the ICU stay.
The optimal duration of ICU admission has not
been identified. Additional areas for further
research include the impact of critical care on
quality of life (Darmon and Azoulay, 2009).
The most common reasons for ICU admission
in patients with cancer include respiratory
failure, postanesthesia recovery, infection and
sepsis, bleeding, and oncologic emergencies
(Shelton, 2010). This chapter will address
critical care of oncology patients with
hematologic,
infectious,
and
structural
complications of cancer or its treatment.
Sepsis in the immunocompromised host
Physiologic guidelines
A normal neutrophil count is approximately
65% of the total white blood cell count. A
577
neutrophil count of less than 2500/mm3 is
considered abnormal. The risk for infection
increases as the neutrophil count decreases.
Severe neutropenia is defined as an absolute
neutrophil count (ANC) of less than 500/mm3.
Patients with an ANC < 100/mm3 are at
greatest risk for infection. See Box 11.1 for
calculation of the ANC. A patient may have a
normal or high total white blood cell (WBC)
count and be neutropenic; therefore, the ANC
should always be calculated in at-risk patients.
In addition to the neutrophil count, the
duration of neutropenia is also a risk factor for
infection; the longer a patient is neutropenic,
the greater the risk for infection. In the
oncology population, common causes of
neutropenia include hematologic malignancies
such as leukemia, myelodysplastic syndrome,
lymphoma, myeloma; and chemotherapy, and
radiation therapy to the pelvis, sternum, or
femur.
Box 11.1 Calculating the absolute
neutrophil count (ANC).
Example: WBC = 3.0 or 3000; segs = 5 and
bands = 0
578
3000 × (5 + 0)/100 = 3.0 × 0.05 = 150
The incidence of febrile neutropenia in cancer
patients receiving intensive chemotherapy is
between 70 and 100% (Danai et al., 2006;
Moerer and Quintel, 2009). Due to the high risk
for infection in this population, sepsis is a
common complication and is a leading cause of
nonrelapse mortality (Penack et al., 2011).
Different sources have published definitions for
sepsis which include an elevated WBC count. In
the neutropenic patient, this criterion cannot be
used to define sepsis. Therefore, any
neutropenic patient with signs of a systemic
inflammatory response that cannot be
attributed to another cause (such as drug fever
or transfusion reaction) should be presumed to
have sepsis (Penack et al., 2011). Negative
blood cultures should not reduce suspicion of
sepsis as only 30% of patients with febrile
neutropenia have culture-proven bloodstream
infections (Feld, 2008; Penack et al., 2007).
In addition to severity and duration of
neutropenia, other risk factors for neutropenic
sepsis include disruptions in mucosal barriers
from mucositis, central venous catheters, and
invasive procedures. The incidence of infection
is higher in patients with poor nutritional status
(Penack et al., 2011). In the neutropenic
patient, fever is defined as a single oral
579
temperature of 100.9 °F (38.3 °C) or a
temperature of 100.4 °F (38 °C) sustained for
1 h (Legrand et al., 2011). The presence of
shaking chills should also warrant an evaluation
for fever and infection.
Infections
are
commonly
caused
by
gram-negative or gram-positive organisms.
Escherichia coli, Pseudomonas aeruginosa,
and Klebsiella pneumonia are the most
common gram-negative organisms to cause
infection
in
the
neutropenic
host.
Coagulase-negative
staphylococci,
Staphylococcus aureus, and streptococci are
the most common gram-positive organisms
(Klastersky et al., 2011). With increasing use of
central venous catheters, gram- positive
organisms are assuming prominence.
Assessment and monitoring in
neutropenic patients
In neutropenic patients, a fever or chills is often
the only sign of infection. Neutropenic patients
cannot exhibit pus, sputum, or pulmonary
infiltrates, or WBCs on a urinalysis. Clinical
signs of infection will be much more subtle and
require a careful, astute assessment. The skin
must be examined carefully for any breaks in
integrity, for rashes that may signal fungal,
viral, or bacterial infections, and for changes in
the appearance of line insertion sites. Central
line infections may manifest only as tenderness
580
or mild erythema at the insertion site. The oral
mucosa should be examined with good light for
the presence of erythema, oral thrush or
lesions, and thickened or scant saliva. The
perirectal area should also be examined
carefully for erythema, induration, tenderness,
and breaks in skin integrity. However, a rectal
exam should never be performed in a
neutropenic host. Any disruption in the
mucosal barrier in the rectum can result in
severe, life-threatening infections.
The assessment of abdominal pain in a
neutropenic patient can be challenging.
Necrotizing entercolitis or typhlitis can be a
life-threatening complication of neutropenia.
No clinical criteria for diagnosis have been
established; however, fever and abdominal pain
in the presence of neutropenia should raise
suspicion.
Bowel
wall
thickening
on
radiographic imaging can confirm suspicion. In
a cohort study of 60 patients, median time from
last chemotherapy to development of
abdominal pain was 10 days. Hypotension and
diarrhea were also associated with necrotizing
enterocolitis. The 30- and 90-day mortality
rates were 30 and 52%, respectively. Duration
of neutropenia, lack of surgical intervention,
and presence of severe sepsis led to a poorer
overall survival rate (Badgwell et al., 2008).
581
Neutropenia management
When a neutropenic patient develops a fever,
the infectious workup must begin promptly.
Blood cultures should be obtained as soon as
possible, including one set of peripheral blood
cultures and one set of blood cultures obtained
from a central line, if present (Schiffer et al.,
2013). A urine culture should also be obtained.
Once blood cultures are obtained, empiric
antibiotics should begin immediately. The
process of blood drawing and antibiotic
initiation should be completed within 1 h of
fever presentation. Stool cultures and
cerebrospinal fluid samples should be obtained
based on clinical suspicion (Halfdanarson,
Hogan, and Moynihan, 2006). A chest
radiograph is often part of the febrile workup.
However, findings are often negative.
Use of empiric antibiotics with broad- spectrum
coverage is recommended. Antibiotics should
continue until the neutrophil count recovers to
over 500/μl for 2 days and for 48 h after fever
resolution
(Legrand
et
al.,
2011).
Administration of effective antimicrobial
therapy within the first hour of observed
hypotension is associated with increased
survival. In a study of more than 2000 patients,
each hour of delay in antibiotic administration
resulted in a 7.6% average decrease in survival
(Kumar et al., 2006).
582
Monotherapy with a broad-spectrum antibiotic
is as effective as dual therapy for gram-negative
organisms and has fewer side effects.
Acceptable drug choices for monotherapy
include cefipime, ceftazidime, or carbapenem
(Halfdanarson, Hogan, and Moynihan, 2006;
Klastersky et al., 2011). Use of agents with
gram-positive coverage should be considered in
patients with known colonization with
gram-positive bacteria, patients with central
venous access devices, patients with skin or
mucosal damage, patients with hypotension,
and in patients who received prophylactic
antibiotics
for
gram-negative
bacteria
(Halfdanarson, Hogan, and Moynihan, 2006).
Vancomycin is the common drug of choice for
empiric gram-positive coverage. Indwelling
catheters should be removed if the catheter is
the suspected source of infection (Legrand et
al.,
2011).
Combination
therapy
with
beta-lactams and an aminoglycoside may be
appropriate for infections caused by resistant
organisms such as P. aeruginosa or in patients
at high risk for complications (Klastersky et al.,
2011). Antifungal coverage should be
considered in a patient on empiric antibiotics
with persistent fever for 5 days or more.
Persistent fever with signs of clinical
deterioration warrant a complete reassessment
and collection of new culture data to look for
new sources of infection (Legrand et al., 2011)
(see Fig. 11.1). Causes of persistent fever include
583
inappropriate antibiotic dosing, Clostridium
difficile
infection,
antibiotic-resistant
organisms,
fungal
infections,
parasitic
infections (e.g., Toxoplasma gondii), viral
infections
including
herpesviruses,
parainfluenza, respiratory syncytial virus, and
influenza viruses; persistent focus of infection
(such as an indwelling catheter); and
noninfectious
causes
including
blood
transfusions, venous thrombosis, drug-induced
fever, graft-versus-host disease (GVHD),
underlying malignancy, pancreatitis, and
hemophagocytic lymphohistiocytosis (Legrand
et al., 2011). The expected or median time to
fever resolution in hospitalized patients with
cancer is 5–7 days (Legrand et al., 2011).
584
Figure 11.1 Suggested adjustments to the
empirical antibiotic regimen after 3–5 days
treatment.
Source: Legrand, M., Max, A., Schlemmer, B., &
Gachot, B. (2011). Annals of Intensive Care, 1, p.
6.
Evidence-based guidelines
In 2010, the German Society of Hematology
and Oncology published guidelines on the
management of sepsis in neutropenic patients
(Penack et al., 2011). These guidelines
recommend empiric antimicrobial therapy with
meropenem, imipenem/cilastin, or piperacillin/
tazobactam monotherapy. The addition of an
aminoglycoside is not recommended due to
increased toxicity without added efficacy. Once
an organism is identified, antimicrobial
selection should be targeted to that organism.
Early goal-directed therapy is recommended to
restore cardiac function and improve survival.
Studies have demonstrated increased survival
of patients with sepsis when interventions are
initiated within the first 6 h (Dellinger et al.,
2013; Penack et al., 2011). Interventions
include volume resuscitation with crystalloids
or colloids to a mean arterial pressure of at least
65 mmHg, central venous pressure of
8–12 mmHg, pulmonary wedge pressure of
12–15 mmHg, urinary output of at least 0.5 ml/
kg/h, and central or mixed venous oxygen
585
saturation of 70% or more. Use of albumin is
not recommended as there have been no studies
demonstrating efficacy. If fluid resuscitation
does not achieve these parameters, treatment
with vasopressors, specifically norepinephrine,
is indicated. There is no role for sodium
bicarbonate therapy in the presence of lactic
acidosis and pH > 7.15.
For the treatment of pulmonary failure, Penack
et al. (2011) recommend the use of continuous
positive airway pressure (CPAP) in a patient
who is awake and cooperative with minor
disturbances in gas exchange defined as a
PaO2/FiO2 of more than 200. Noninvasive
ventilation is preferred when feasible and
initiated early as studies have demonstrated
decreased need for intubation in the oncology
population. Failure of noninvasive ventilation
has been reported in 50% of critically ill
hematology patients and is associated with
increased mortality (Azoulay et al., 2004).
Diagnostic bronchoscopy with bronchoalveolar
lavage is not indicated as the diagnostic yield is,
at best, 50% and often leads to mechanical
ventilation, decreasing the chances for survival
(Hummel et al., 2008b; Rabbat et al., 2008).
There are no specific recommendations related
to management of renal dysfunction as there
are no clear guidelines for the initiation of renal
replacement therapy in the setting of
neutropenic sepsis.
586
Nutritional recommendations include use of
enteral over parenteral nutrition with an intake
not exceeding 20–25 kcal/kg of ideal body
weight until the recovery phase when intake can
increase to 30 kcal/kg. Blood glucose levels
should be maintained at less than or equal to
150 mg/dl. In non-neutropenic patients,
glucocorticoids are a component of early
goal-directed
therapy.
However,
this
intervention has not been studied prospectively
in the neutropenic population and is not
recommended by this group (Penack et al.,
2011). Similarly, activated protein C (APC) has
been used effectively in non-neutropenic sepsis;
however, the use of APC in the neutropenic
population
is
often
not
feasible
as
thrombocytopenia
usually
accompanies
neutropenia and APC is contraindicated with a
platelet count of less than 30 000/μl. In
patients with higher platelet counts, APC is
recommended in patients with APACHE II
scores of over 25 and at least two organs failing.
Routine use of growth factors such as
granulocyte colony-stimulating factor (GCSF) is
not recommended. In 2010, the European
Organisation for Research and Treatment of
Cancer (EORTC) updated guidelines for the use
of GCSF to reduce the incidence of
chemotherapy-induced febrile neutropenia in
adult patients with cancer (Aapro et al., 2011).
Regarding the use of GCSF in patients with
existing febrile neutropenia, the EORTC
587
recommends the following: “Treatment with
G-CSF for patients with solid tumours and
malignant lymphoma and ongoing FN is
indicated only in special situations. These are
limited to those patients who are not
responding
to
appropriate
antibiotic
management and who are developing
life-threatening infectious complications (such
as severe sepsis or septic shock)” (Aapro et al.,
2011, p. 21).
In 2009, the Infectious Diseases Society of
America updated their clinical practice
guidelines for the management of candidiasis.
For neutropenic patients, empiric treatment for
suspected invasive candidiasis should include
caspofungin (loading dose of 70 mg, then 50 mg
daily), lipid formulation Amphotericin B
(3–5 mg/kg daily), or voriconazole (6 mg/kg
intravenous [IV] twice daily for two doses then
3 mg/kg twice daily) (Pappas et al., 2009). For
documented candidemia in neutropenic
patients, an echinocandin such as caspofungin,
micafungin, or anidulafungin or lipid
formulation Amphotericin B is recommended
(Pappas et al., 2009). For prevention of
candidal
infections
in
patients
with
chemotherapy-induced neutropenia or patients
undergoing stem cell transplant, fluconazole
400 mg daily, posaconazole 200 mg three times
daily, or caspofungin 50 mg daily is
recommended (Pappas et al., 2009).
588
Research
Identification of biomarkers that may predict
risk of severe infection in febrile neutropenic
patients is being evaluated. Procalcitonin (PCT)
and C-reactive protein (CRP) may be useful
markers. In patients with hematologic
malignancy, elevated PCT but not CRP was
found to be predictive of severe infection
(Massaro et al., 2007). Other cytokines such as
interleukin 6 and interleukin 8 are also under
investigation.
Stem cell transplant
Hematopoietic stem cell transplant (HSCT) is
being used more frequently in the management
of malignant illnesses. HSCT is a general term
that includes bone marrow, peripheral blood,
and cord blood as the possible sources of stem
cells. Autologous transplant involves collecting
and reinfusing the patient’s own stem cells.
Autologous transplant allows the delivery of
high-dose chemotherapy and uses the patient’s
own stem cells to rescue the bone marrow and
shorten the time to marrow recovery.
Autologous stem cell transplant is most
commonly used in the management of patients
with lymphoma and multiple myeloma.
Syngeneic transplant uses stem cells from an
identical twin. Allogeneic transplant uses stem
cells from a human leukocyte antigen (HLA)
matched donor (Saria and Gosselin-Acomb,
589
2007).
Allogeneic
transplant
involves
administration of high doses of chemotherapy
and/or total body radiation in order to treat the
underlying malignancy and make space for the
new donor cells to grow or engraft (Rimkus,
2009). The conditioning treatment can cause
organ
damage.
Additionally,
the
immunosuppressive effects of treatment
increase the risk for life-threatening infection.
Allogeneic transplant is used to treat patients
with leukemia, aplastic anemia, lymphoma,
and, less frequently, multiple myeloma.
At least 15–40% of transplant patients will
require critical care at some point during their
transplant course (Afessa et al., 2003).
Estimated mortality rates for HSCT patients
admitted to the ICU range from 72 to 100%
(Kasberg, Brister, and Barnard, 2011). Patients
receiving autologous transplants have much
lower mortality rates (5–10%) but higher
relapse rates. Some studies suggest that early
ICU admission may reduce mortality (Kasberg,
Brister, and Barnard, 2011). Risk factors for
mortality have been identified and include the
need for mechanical ventilation, vasopressor
support for more than 4 h; higher number of
comorbidities, and other organ damage
(Kasberg, Brister, and Barnard, 2011). Prior to
transplant, the potential risks of the procedure
are explained to the patient in detail. The goal
of allogeneic transplant is to cure the
underlying disease and regain an acceptable
590
quality of life (Saria and Gosselin-Acomb,
2007). Risk factors for post-transplant
complications include renal or other organ
disease, older age, obesity, donor type (match
versus mismatch), and underlying disease
(Rimkus, 2009). Complications requiring
intensive care include infection, GVHD, hepatic
veno-occlusive disease (VOD), and respiratory
complications (Saria and Gosselin-Acomb,
2007). The risk for particular complications
changes over time. These complications will be
briefly discussed here.
Infection
Agents used for conditioning prior to infusion
of
stem
cells
result
in
profound
myelosuppression. In addition, many of these
agents result in inflammation and disruption of
the gastrointestinal mucosa (Rimkus, 2009).
Prophylactic antimicrobials including antiviral,
antifungal, and antibacterial agents are
commonly used to mitigate the risk of invasive
infection. Despite advances in prophylactic
strategies and supportive care, infection
remains a leading cause of morbidity and
mortality (Martin-Peña et al., 2010). In a
prospective study of infectious complications in
allogeneic stem cell transplant recipients, the
incidence of infection was 1.36 episodes per
patient in the first year post transplant
(Martin-Peña et al., 2010). Risk for infection is
highest during the pre-engraftment period and
591
in the late phases post transplant (Martin-Peña
et al., 2010).
Fever during the period of neutropenia is
managed as described earlier in the section
“Neutropenic
Fever.”
Catheter-related
bloodstream infections, bacteremia, and
pneumonia are the most common types of
infection in the pre-engraftment period
(Martin-Peña et al., 2010). However, even after
the neutrophil count recovers, allogeneic stem
cell transplant recipients remain at high risk for
infection due to the use of immunosuppressive
medications to decrease the incidence of
GVHD, as well as delayed lymphocyte and
immunoglobulin level recovery (Kasberg,
Brister, and Barnard, 2011). In the late phase
post transplant, the presence of GVHD is a
primary risk factor for development of
infections (Martin-Peña et al., 2010).
Graft-versus-host disease
GVHD results when the donor’s immune
system, specifically the T cells, recognizes the
patient’s body tissues as foreign and mounts an
inflammatory reaction. GVHD may be acute or
chronic, with acute GVHD occurring within the
first 100 days post transplant and chronic
GVHD occurring after 100 days. GVHD is
suspected based on clinical findings and timing
of presentation, and can be confirmed by tissue
biopsy (Kasberg, Brister, and Barnard, 2011).
Severity is described by a grading and staging
592
system. Acute GVHD develops as a result of
tissue damage from the conditioning regimen,
which stimulates the release of cytokines, which
in turn activate donor T cells, resulting in tissue
destruction and necrosis (Kasberg, Brister, and
Barnard, 2011). Development of moderate to
severe GVHD is associated with a higher
mortality rate, with acute GVHD accounting for
15–40% of deaths (Kasberg, Brister, and
Barnard, 2011).
Acute GVHD involves the skin, gut, or liver.
Acute GVHD of the skin is most common and
manifests as a maculopapular rash, which may
be pruritic (Kasberg, Brister, and Barnard,
2011). Hepatic GVHD is the second most
common and manifests as abnormal liver
function, specifically elevations in conjugated
bilirubin and alkaline phosphatase. Acute
GVHD of the gut is marked by diarrhea and
abdominal discomfort (Kasberg, Brister, and
Barnard, 2011; Newman, 2000).
Immunosuppressive
agents
including
calcineurin
inhibitors
(cyclosporine,
tacrolimus), methotrexate, and antithymocyte
globulin are used prophylactically to decrease
the risk of GVHD. Once GVHD develops,
corticosteroids are the mainstay of treatment.
Other agents used include rituximab,
daclizumab,
infliximab,
sirolimus,
and
mycophenolate mofetil, and photopheresis may
be used to treat acute GVHD (Kasberg, Brister,
593
and Barnard, 2011; Saria and Gosselin-Acomb,
2007).
Chronic GVHD can involve any organ or tissue
type and is marked by dryness and fibrotic
complications (Saria and Gosselin-Acomb,
2007). Chronic GVHD results from donor T
cells inducing autoantibodies resulting in an
“autoimmune-like state” (Kasberg, Brister, and
Barnard, 2011, p. 357). The biggest risk factor
for the development of chronic GVHD is the
occurrence of acute GVHD. Chronic GVHD may
occur as an extension of acute GVHD, occur
after acute GVHD has resolved, or occur in the
absence of acute GVHD. The most common
organs involved with chronic GVHD include the
skin, lungs, and liver (Kasberg, Brister, and
Barnard, 2011). Chronic GVHD is classified
differently than acute GVHD and is based on
the number and extent of organs involved
(Pallera & Schartzberg, 2004). (see Table 11.3).
Management of chronic GVHD uses similar
strategies and medications used to treat acute
GVHD. High-dose steroids are typically used in
first-line management (e.g., 2 mg/kg/day) with
tapering of steroids once symptoms improve
(Kasberg, Brister, and Barnard, 2011). Other
agents as described earlier may be used in
combination; however, the ideal combination
has not yet been identified (Kasberg, Brister,
and Barnard, 2011; Newman, 2000).
594
Hepatic veno-occlusive disease
Hepatic VOD, also known as sinusoidal
obstructive syndrome (SOS), involves central
venular occlusion and endothelial injury
resulting
in
hepatocyte
necrosis
and
interparenchymal fibrosis (Coppell, Brown, and
Perry, 2003; Kasberg, Brister, and Barnard,
2011). Chemotherapy causes endothelial injury
resulting in cytokine release (Coppell, Brown,
and Perry, 2003). This complication occurs in
5–60% of transplant patients (Richardson et
al., 2012). It is an early complication and
severity
ranges
from
self-limiting
to
life-threatening. Mortality from severe VOD
exceeds 50% (Richardson et al., 2012). The
diagnosis of VOD is based on a classic triad of
weight gain, tender hepatomegaly, and jaundice
(Tuncer et al., 2012). Symptoms most
commonly present within the first 3 weeks after
transplant. Risk factors for the development of
VOD/SOS include pre-existing liver disease;
history of VOD/SOS; hepatic radiation; recent
use of gemtuzumab ozogamicin; condition
regimens containing high-dose total body
irradiation
(>14 Gy),
cyclophosphamide,
busulfan, melphalan; or concomitant use of
sirolimus during conditioning (Tuncer et al.,
2012).
Clinical features include weight gain, increased
abdominal girth, severe right upper quadrant
pain, and hyperbilirubinemia. On exam, ascites
595
and painful hepatomegaly may be present
(Tuncer et al., 2012). Coagulation factor
deficiencies and thrombocytopenia refractory to
platelet transfusions may also be present (Saria
and Gosselin-Acomb, 2007; Tuncer et al.,
2012). Weight gain may be unresponsive to
diuretics. Renal dysfunction may develop as a
result of hepatorenal syndrome, seen in 50% of
patients with SOS (Tuncer et al., 2012).
Transjugular liver biopsy is the gold standard
diagnostic test; however, this may be
contraindicated in patients with severe
coagulopathy or thrombocytopenia (Saria and
Gosselin-Acomb, 2007).
Prevention of VOD is critical as there are no
effective treatments for VOD. Modification of
risk factors including reducing chemotherapy
doses and fractionating total body irradiation
may decrease the incidence of VOD. Supportive
treatment
includes
ursodiol,
analgesia,
avoidance of nephrotoxins and hepatotoxins,
aggressive fluid management, and blood
product support (Johnson and Savani, 2012;
Kasberg, Brister, and Barnard, 2011; Zhang,
Wang, and Huang, 2012). Antithrombin III,
prostaglandin E1, defibrotide, and heparin have
been examined in the prophylactic setting;
however, none of these agents effectively
decreased the risk of VOD/SOS development
(Johnson and Savani, 2012; Richardson et al.,
2012; Zhang, Wang, and Huang, 2012).
596
The goal of supportive care in patients who
develop VOD/SOS is to maintain intravascular
volume and optimize renal perfusion without
causing fluid volume overload (Tuncer et al.,
2012). Use of diuretics to manage fluid volume
overload, paracentesis to manage large volume
ascites, and hemodialysis may be used as
clinically indicated (Richardson et al., 2012).
There are no effective, evidence-based
strategies for treating patients with severe
VOD/SOS (Richardson et al., 2012; Tuncer et
al., 2012). Defibrotide has demonstrated
efficacy in treating VOD/SOS and improving
survival in Phase II and III trials (Richardson et
al., 2012). However, there have been no
prospective, randomized controlled trials
examing the use of defibrotide in VOD
management. Defibrotide is currently only
available through a treatment investigational
new drug (IND) study in the United States
(Richardson et al., 2012).
Pulmonary complications
Noninfectious pulmonary complications affect
between 21 and 35% of allogeneic transplant
patients (Kasberg, Brister, and Barnard, 2011).
Complications include pulmonary edema,
diffuse alveolar hemorrhage (DAH), idiopathic
pneumonia syndrome, bronchiolotis obliterans
organizing pneumonia, and pulmonary fibrosis
(Kasberg, Brister, and Barnard, 2011; Saria and
Gosselin-Acomb, 2007).
597
Respiratory complications are the most
common cause of mortality in the transplant
population (Sharma et al., 2005). Development
of respiratory failure requiring mechanical
ventilation is associated with a poor prognosis
(Kasberg, Brister, and Barnard, 2011).
DAH is characterized by cough, dyspnea,
hypoxia, respiratory compromise, and fever
without evidence for infection (Afessa, 2011a;
Saria and Gosselin-Acomb, 2007). Hemoptysis
is uncommon (Afessa, 2011a). DAH most
commonly occurs within the first 30 days after
transplant and carries a mortality rate of 76%
(Afessa, 2011a). Bronchoscopy may establish
the diagnosis. On chest radiograph, unilateral
or bilateral alveolar infiltrates may be seen.
Admission to the ICU and use of mechanical
ventilation is usually warranted (Afessa, 2011a;
Saria and Gosselin-Acomb, 2007). Management
includes use of steroids to mediate
inflammation (Saria and Gosselin-Acomb,
2007). The optimal steroid dose and schedule
has not been identified (Afessa, 2011a). There
are no prospective, randomized trials
examining treatment of DAH in the transplant
setting (Afessa, 2011a).
The idiopathic pneumonia syndrome (IPS) is
usually a diagnosis of exclusion (Saria and
Gosselin-Acomb, 2007). Afessa (2011b) states
that “IPS is characterized by clinical features of
pneumonia and diffuse lung injury in the
598
absence of an identified infection” (p. 7). IPS is
seen between days 21 and 87 post allogeneic
stem cell transplant and carries a mortality rate
up to 82% (Afessa, 2011b; Saria and
Gosselin-Acomb, 2007). Risk factors include
older age, total body irradiation, GVHD, +CMV
(cytomegalovirus) serology of the donor,
diagnosis
other
than
leukemia,
and
pretransplant conditioning (Afessa, 2011b).
Clinical symptoms may vary in intensity from
asymptomatic to acute respiratory distress and
may include dyspnea, dry cough, hypoxemia,
and tachypnea (Saria and Gosselin-Acomb,
2007). Radiographic findings reveal diffuse,
bilateral infiltrates (Afessa, 2011b; Saria and
Gosselin-Acomb, 2007). Diagnosis may be
confirmed
by
bronchoscopy
with
bronchoalveolar lavage. Other than supportive
care, there are no definitive interventions (Saria
and Gosselin-Acomb, 2007).
Bronchiolitis obliterans occurs in 10–15% of
HSCT patients and is seen in patients who have
developed chronic GVHD. Bronchiolitis
obliterans syndrome (BOS) is defined as a fixed
airflow obstruction that occurs within the first 2
years after allogeneic stem cell transplant
(Bacigalupo et al., 2012). The prognosis is poor,
with a 5-year survival of 15% (Bacigalupo et al.,
2012). Clinical symptoms may include
recurrent sinus and bronchial infections.
Chronic cough unexplained by other causes is
common (Saria and Gosselin-Acomb, 2007).
599
Pulmonary function tests are the gold standard
for
diagnosis
and
reveal
bronchodilator-resistant airway obstruction.
The National Institutes of Health developed
BOS diagnostic criteria, which include
FEV1 < 75% and FEV1/VC ratio over 0.7
(Bacigalupo et al., 2012). Treatment should be
initiated once these criteria are met. Treatment
involves immunosuppressive agents, such as
steroids; however, many do not respond to
therapy. Prednisone, 1 mg/kg of body weight,
given once daily for 2 weeks with taper over 4
weeks is suggested (Bacigalupo et al., 2012).
BOS often develops in the setting of
immunosuppression tapering. Reinitiation of
immunosuppression, such as tacrolimus or
sirolimus, may be recommended (Bacigalupo et
al., 2012). Bronchodilators and inhaled steroids
may be used as an adjunct to systemic therapy
(Bacigalupo et al., 2012).
Hematologic complications
Hemorrhagic complications
Patients with solid tumors and hematologic
malignancies
may
experience
bleeding
complications that require critical care.
Bleeding may result from thrombocytopenia,
coagulation defects, or tumor invasion of blood
vessels. Bleeding may manifest as localized
bleeding or generalized bleeding. Appropriate
600
management should target the underlying
cause.
Thrombocytopenia
Thrombocytopenia is a common hematologic
disorder in patients with cancer and is a
common occurrence in the ICU, associated with
a longer length of stay and increased mortality
(Baughman et al., 1993). Thrombocytopenia is
caused by one of three possible mechanisms: (1)
decreased platelet production, (2) increased
platelet destruction, or (3) sequestration in the
spleen. Decreased platelet production may
result from nutritional deficiencies such as
vitamin B12 or folate deficiency, or a disorder
affecting bone marrow function including
aplastic anemia, acute myeloid or lymphoid
leukemias,
myelodysplastic
syndrome,
lymphoma, or multiple myeloma. Decreased
platelet production may also result from
treatment with myelosuppressive agents,
including chemotherapy and radiation therapy
(see Box 11.2). Thrombocytopenia resulting
from myelosuppressive therapy is usually
predictable, occurring 6–14 days after
treatment, and recovers 1–3 weeks following
completion of therapy (Vadhan-Raj, 2009).
Increased platelet destruction is seen in
disorders such as disseminated intravascular
coagulation
(DIC),
thrombotic
thrombocytopenia purpura (TTP), immune
601
thrombocytopenia purpura (ITP), medications,
sepsis, and infection.
Box 11.2 Chemotherapeutic
treatments associated with
thrombocytopenia (Fischer et al.,
2003; Jardim et al., 2012).
Carboplatin
Dacarbazine
Fluorouracil
Doxorubicin and Ifosfamide
Fludarabine
Ifosfamide, Carboplatin, and Etoposide (ICE)
Mesna, Doxorubicin, Ifosfamide,
Dacarbazine (MAID)
Melphalan
Mitomycin
Nitrosureas (Carmustine; lomustine)
Oxaliplatin
Streptozocin
Thiotepa
In drug-induced thrombocytopenia, there is an
abrupt onset of severe thrombocytopenia (<20
602
000), usually with clinically relevant bleeding.
Platelet recovery is seen within 1–2 days after
drug discontinuation. See Box 11.3 for
nonchemotherapy agents that may cause
thrombocytopenia (George and Aster, 2009).
Splenic sequestration may be seen in
lymphoma, chronic lymphocytic leukemia, and
myeloproliferative disorders. Patients may have
more than one cause of thrombocytopenia at a
given time (Carlson and DeSancho, 2010). The
following will focus on thrombocytopenia
resulting from cancer or anticancer therapies.
Box 11.3 Nonchemotherapy drugs
associated with
thrombocytopenia development
(Sekhon and Roy, 2006).
Abciximab
Acetominophen
Carbamazepine
Chlorpropamide
Cimetidine
Danazol
Diclofenac
Digoxin
603
Efalizumab
Eptigibatide
Gold
Hydrochlorothiazide
Interferon-alpha
Methyldopa
Nalidixic acid
Quinidine
Quinine
Penicillins
Ranitidine/Rifampin
Tirofiban
Trimethprim/sulfamethoxazole
Vancomycin
Monitoring elements
In order to identify the cause of
thrombocytopenia, a thorough history must be
obtained from the patient including the onset,
duration, severity, and type of bleeding
symptoms. A detailed review of the patient’s
medication list must also be obtained in order
to identify agents that may be causing
thrombocytopenia.
604
A complete blood count including the platelet
count
should
be
obtained.
However,
examination of the peripheral blood smear is a
critical component in identifying causes of
thrombocytopenia. In some instances, when
using automated counting machines, platelet
clumping
may
be
mistaken
for
thrombocytopenia. When examined under a
microscope, platelet clumping is easily
identified. Examination of the peripheral smear
may reveal schistocytes or microspherocytes,
suggesting a destructive process (Carlson and
DeSancho, 2010).
Spontaneous bleeding is not typically seen
unless the platelet count is less than 10 000/
mm3. In patients with fever, sepsis, trauma, or
untreated hematologic malignancy, bleeding
may be seen at higher platelet counts. The most
common site of bleeding is mucocutaneous
including wet purpura, bleeding gums,
petechiae,
ecchymoses,
epistaxis,
gastrointestinal, or genitourinary bleeding
(Carlson and DeSancho, 2010).
A thorough assessment including examination
of the oral and nasal mucosa, skin, wounds,
peripheral puncture sites, and central line entry
sites for signs of bleeding should be conducted
at least every 8 h. Examination of sputum,
emesis, stool, urine, and any other drainage
should be examined for occult and visible
blood. A neurologic examination should be
605
performed
regularly.
A
patient
with
thrombocytopenia who complains of a new
headache must undergo thorough evaluation
for bleeding in the central nervous system as a
headache may be the only warning sign.
Changes in neurologic examination should also
warrant a radiologic evaluation for bleeding.
Management
In cases of thrombocytopenia due to infection,
sepsis, or DIC, the underlying cause must be
identified and treated. In patients with
thrombocytopenia due to a hematologic
malignancy, bone marrow metastasis from a
solid tumor, or a side effect of myelosuppressive
therapy, bleeding must be prevented and
managed supportively until the underlying
disease is treated or until the bone marrow
function recovers.
Platelet transfusion is the most effective
treatment
for
patients
with
severe
thrombocytopenia
(Vadhan-Raj,
2009).
However, there are no evidence-based
guidelines outlining the best, safest parameter
for platelet transfusion. Patients who are
afebrile and asymptomatic may not require
platelet transfusion unless the platelet count is
less than 10 000/mm3. Studies have indicated
that a platelet threshold of 10 000/mm3 is safe
and well tolerated (Benjamin and Anderson,
2002). In febrile or septic patients, or in
606
patients undergoing treatment for leukemia,
transfusion may be required if the platelet
count is less than 20 000/mm3. For patients
who are experiencing bleeding or require an
invasive procedure such as placement of a
central venous catheter, biopsy, lumbar
puncture, thoracentesis, or paracentesis,
platelet count should be maintained above 50
000/mm3 (Carlson and DeSancho, 2010).
Platelet transfusions are available in different
formulations including pooled donations,
single-donor platelets, and HLA-matched
platelets. Patients who have never received
platelet transfusions before can be treated with
pooled donations. If a platelet transfusion does
not achieve the expected increase in platelet
count (10 000 unit increase for every 1 unit
transfused) or does not improve bleeding, one
should suspect either continued platelet
consumption,
splenic
sequestration,
or
alloimmunization (Carlson and DeSancho,
2010). Alloimmunization occurs when the
patient’s immune system recognizes the
antigens on donated platelets as foreign and
clears them from circulation. This concept can
be tested by sending blood to the blood bank or
the American Red Cross where they look for the
presence of antiplatelet antibodies. Measuring
the platelet count 1 h and 24 h after transfusion
may also be helpful. If the 1 h platelet count is
increased but not maintained at 24 h, a
607
persistent consumptive or hemorrhagic process
is likely. If neither the 1 h nor the 24 h count is
increased, alloimmunization is the likely
problem (Carlson and DeSancho, 2010). When
alloimmunization has occurred, single-donor
platelets or HLA-matched platelets will be
necessary to appropriately increase the platelet
count.
In
patients
with
hematologic
malignancies or in patients who have
undergone organ or stem cell transplants,
irradiated platelets must be transfused in order
to minimize the risk for transfusion-associated
GVHD (Rühl, Bein, and Sachs, 2008; Treleaven
et al., 2012).
A number of cytokines have been studied in the
setting
of
chemotherapy-induced
thrombocytopenia in an effort to stimulate
thrombopoesis. However, these agents have
had only modest efficacy with unacceptable
toxicity (Vadhan-Raj, 2009). Agents such as
recombinant thrombopoeitin (TPO) and
TPO-receptor agonists have been used
effectively to treat ITP; however, use in
chemotherapy-induced thrombocytopenia has
not yet been established.
Thrombotic microangiopathy
Physiologic guidelines
Thrombotic microangiopathy (TMA) is a group
of disorders characterized by microvascular
thrombosis, thrombocytopenia, and end-organ
608
damage (Blake-Haskins, Lechleider, and
Kreitman, 2011). TMA includes TTP and
hemolytic uremic syndrome (HUS). TTP and
HUS are two distinct disorders, both involving
microvascular damage and platelet destruction.
TTP has classically been defined as a pentad of
clinical symptoms including fever, anemia,
thrombocytopenia, renal insufficiency, and
neurologic changes. However, a minority of
patients present with the entire pentad
(Levandovsky et al., 2008). George (2009)
suggested that TTP be redefined as adults with
“thrombocytopenia
and
microangiopathic
hemolytic anemia without an alternative
etiology” (p. 75) and that the term HUS be
reserved for children with these symptoms as
well as renal dysfunction. HUS is often
preceded by a diarrheal illness and is
characterized by microangiopathic hemolytic
anemia, low platelets, and a clinical picture
marked by renal insufficiency (Levandovsky et
al., 2008). The diagnosis of TTP is reserved for
situations
where
neurologic
symptoms
predominate in comparison to HUS, in which
renal
dysfunction
predominates
(Blake-Haskins, Lechleider, and Kreitman,
2011). TTP and HUS associated with cancer or
cancer therapies are characterized by both
microvascular and macrovascular thrombus
formation in comparison to idiopathic or
human
immunodeficiency
virus
(HIV)-associated disease, which is primarily
microvascular with platelet-rich thrombosis.
609
Causes of TMA include medications, such as
estrogen, quininine, cyclosporine, tacrolimus,
ticlodipine,
and
clopidogrel;
infections
including E. coli 0157:H7, HIV, and
pneumococcus; and idiopathic causes including
pregnancy, autoimmune disorders, and stem
cell transplant. Approximately, 3–15% of
patients who develop TTP/HUS have an
underlying malignancy (Benoit and Hoste,
2010). If a patient presents with TTP/HUS
without a cancer diagnosis, a thorough
evaluation for underlying malignancy should be
employed, especially if the patient presents with
an elevated lactate dehydrogenase (LDH) or is
refractory to treatment. Cancer populations at
risk for TMA include patients post stem cell
transplant, patients with lung, breast, gastric,
colon, pancreas, and prostate cancers and
lymphomas (Benoit and Hoste, 2010; Carlson
and DeSancho, 2010). Anticancer agents known
to precipitate TTP/HUS include mitomycin-C,
bleomycin,
cisplatin,
gemcitabine,
and
tamoxifen.
Other
medications
include
calcineurin inhibitors, which are frequently
used as immunosuppressive therapy in the
stem cell transplant population.
The pathophysiology of TTP begins with
microvascular damage to endothelial cells with
release of von Willebrand factor (vWF)
molecules. In healthy conditions, vWF
molecules are cleaved by ADAMTS13,
regulating thrombus formation. In TTP, there is
610
a severe deficiency of ADAMT13 (with
ADAMTS13 activity <5% of normal) or an
inhibitor of ADAMTS13 may be present
(Blake-Haskins, Lechleider, and Kreitman,
2011). The development of antibodies that may
act as an ADAMTS13 inhibitor may be induced
by some drugs. If the ultralarge vWF molecules
are not cleaved by ADAMTS13, the vWF
molecules induce platelet aggregation in the
microcirculation in areas of shear stress,
resulting in increased platelet consumption and
red blood cell (RBC) destruction. Platelet
aggregation
results
in
small-vessel
microthrombi formation, which then results in
impaired organ function, manifesting as renal
impairment, respiratory compromise, and
central nervous system impairment. In HUS,
ADAMTS13 activity is usually preserved
(Levandovsky et al., 2008) and there is
selective endothelial damage in the kidneys
(Carlson and DeSancho, 2010).
Recently, an entity called post-transplant TMA
was described as distinctly different from
classic HUS and TTP. Post-transplant TMA is
defined as the presence of microangiopathic
hemolysis with renal and/or neurologic
dysfunction (Ho et al., 2005). There is an
absence of severe ADAMTS13 deficiency and no
evidence of systemic microthrombus formation
(Ruutu et al., 2007). The incidence following
allogeneic stem cell transplant varies from 0.5
to 76% (Fuge et al., 2001; Iacopino et al., 1999;
611
Ruutu et al., 2002). The wide variation in
incidence reflects the lack of a consistent
definition of post-transplant TMA (Ho et al.,
2005). Transplant patients often have anemia,
thromobocytopenia, fever, renal dysfunction,
and schistocytes for other reasons associated
with transplant, which may complicate or
confound the diagnosis of post-transplant TMA
(Ho et al., 2005).
Two groups have developed criteria for defining
post-transplant TMA. The Blood and Marrow
Transplant Clinical Trials Network Toxicity
Committee
Consensus
definition
for
post-transplant TMA includes the presence of
RBC fragments (≥2 schistocytes per high power
field on peripheral blood smear); concurrent
elevated serum LDH; concurrent renal and/or
neurologic dysfunction (renal dysfunction
defined as doubling of serum creatinine or 50%
decrease in creatinine clearance from baseline);
and negative direct and indirect Coombs test
(Ho et al., 2005). The International Working
Group criteria include more than 4%
schistocytes in blood; prolonged or progressive
thrombocytopenia defined as a platelet count
less than 50 × 109/l or 50% or greater decrease
in platelet count; sudden and persistent
increase in LDH; decrease in hemoglobin
concentration
or
increased
transfusion
requirements; and decrease in serum
haptoglobin (Ruutu et al., 2007). The
sensitivity and specificity of the International
612
Working Group criteria exceeds 80% (Ruutu et
al., 2007). Distinguishing the definition of
post-transplant TMA from TTP and HUS is
critical as the treatment is different.
The onset of post-transplant TMA often occurs
within the first 100 days after transplant. The
median time to onset is 44 days with a range of
13–319 days (Ho et al., 2005). Risk factors
include increased age, female sex, unrelated or
mismatched donor, use of calcineurin
inhibitors, use of sirolimus and tacrolimus in
combination, GVHD, and viral or fungal
infections (Ho et al., 2005).
Monitoring elements
TTP occurs more frequently in women (3:2
female to male ratio) and usually occurs in the
fourth decade of life (Coppo and Veyradier,
2012). A characteristic constellation of clinical
signs and symptoms is seen in TTP which may
include fever, anemia, thrombocytopenia, renal
dysfunction,
and
neurologic
symptoms.
Neurologic symptoms are most commonly seen
in 50–80% of cases, and present first, including
headache, vision changes, tinnitus, confusion,
hemiparesis, seizures, and coma (Carlson and
DeSancho, 2010; Coppo and Veyradier, 2012).
A prodrome may precede the above symptoms,
including fatigue, arthralgias, myalgias, and
abdominal or back pain. Cardiac events may be
seen
including
myocardial
infarction,
congestive
heart
failure,
arrhythmias,
613
cardiogenic shock, and sudden cardiac arrest
(Coppo and Veyradier, 2012). Laboratory
evaluation reveals schistocytes on the
peripheral smear (mandatory for diagnosis),
thrombocytopenia and anemia on the complete
blood count, elevated LDH, increased
reticulocyte count, elevated indirect bilirubin,
decreased haptoglobin, and elevated creatinine.
A direct antibody test will be negative.
ADAMT13 activity level may be undetectable in
TTP. Treatment should not be delayed while
waiting for results of this test, as the test may
take more than 24 h to process. Coagulation
parameters are usually normal in TTP/HUS
(Benoit and Hoste, 2010). In HUS, there is no
fever or neurologic changes; the clinical picture
is dominated by renal dysfunction including
elevated creatinine and proteinuria. The patient
may be oliguric. The differential diagnosis for
TTP and HUS includes DIC, prosthetic valve
hemolysis, malignant hypertension, vasculitis,
infection, and Evan syndrome.
Management
Therapeutic plasma exchange (TPE) is the
standard therapy for TTP. Prior to use of
plasma exchange for TTP, mortality rates
exceeded 90%. With the use of plasma
exchange, mortality rates are reduced to less
than 30%. Plasma exchange results in the
removal of ADAMTS-13 inhibitor and replaces
the patient’s plasma with the active enzyme.
614
The goal of plasma exchange is to correct the
platelet count and reverse hemolysis. Complete
response to TPE is defined as a platelet count of
more than 100 000 on two consecutive
evaluations, decreased LDH, and resolution of
neurologic deficits (Levandovsky et al., 2008).
It may take 1–2 weeks to accomplish these
goals. Other authors identify remission as a
normal platelet count for 30 days after
discontinuation of TPE (George, 2009). The
number of plasma exchanges required to
achieve remission is highly variable and may
range from 3 to 89 (George, 2009).
Complications of TPE are usually related to the
central line required to perform the procedure
and include infection and bleeding. Platelet
transfusions should be avoided unless there is
life-threatening bleeding.
Hemodialysis may be appropriate in patients
with renal failure. Neurologic symptoms may
improve before renal function. Other therapies
with known activity include vincristine,
Rituximab, Eculizumab, and IV immune
globulin (Blake-Haskins, Lechleider, and
Kreitman, 2011; Carlson and DeSancho, 2010).
Patients
with
acquired
autoimmune
ADAMTS13 deficiency may also require
immunosuppressive therapy to maintain
remission (George, 2009). Despite known
effective therapies, the prognosis of cancer
patients who develop TTP/HUS is poor.
615
In a cohort study over 24 years with 178
patients, plasma exchange resulted in an 80%
response rate and survival rates over 90%. The
presence of renal insufficiency was associated
with decreased risk for relapse. Longer time to
initial response was associated with increased
risk for relapse. The main predictor of mortality
was the presence of an underlying disorder
(Levandovsky et al., 2008).
Optimal treatment for drug-induced TMA
remains unproven (Blake-Haskins, Lechleider,
and Kreitman, 2011). Prompt discontinuation of
the offending agent is the first step in the
treatment. Case studies have demonstrated safe
use of plasmapheresis and plasma exchange. In
patients refractory or unresponsive to plasma
exchange, eculizumab has demonstrated
efficacy in a small number of cases
(Blake-Haskins, Lechleider, and Kreitman,
2011; Gruppo and Rother, 2009; Nümberger et
al., 2009; Scheiring, Rosales, and Zimmerhackl,
2010). Rituxan has also demonstrated
responses in refractory cases (Blake-Haskins,
Lechleider, and Kreitman, 2011; De La Rubia et
al., 2010).
In post-transplant TMA, the primary
intervention is discontinuation of calcineurin
inhibitor therapy (Ho et al., 2005). Plasma
exchange has not been proven to be effective in
this population (George et al., 2011; Ho et al.,
2005; Ruutu et al., 2007). For drugs such as
616
tacrolimus and cyclosporine, which may be
necessary in the transplant population,
reintroduction at a lower dose may be safe and
may not necessarily result in recurrent or
worsening TMA (Blake-Haskins, Lechleider,
and Kreitman, 2011).
Hyperviscosity syndromes
Physiologic guidelines
Hyperviscosity is defined as “an increased
intrinsic resistance of fluid to flow”
(Halfdanarson, Hogan, and Moynihan, 2006, p.
841). Increased blood viscosity can occur as a
result of malignancies including Waldenstrom
macroglobulinemia (WM), multiple myeloma,
and acute leukemias. In a healthy blood sample,
hematocrit is the most important factor
contributing to serum viscosity and fibrinogen
is the major protein component. In
hyperviscosity syndrome (HVS), excessive
amounts of immunoglobulins, which are large
proteins, are produced. IgM is the largest
immunoglobulin and is the most common cause
of
hyperviscosity.
Waldenstrom
macroglobulinemia is the disorder in which
IgM is produced in abnormally large quantities
(Mullen and Wang, 2007). The proteins
accumulate in the intravascular space, forming
aggregates that increase osmotic pressure and
increase resistance to blood flow. This leads to
microvascular congestion, decreased tissue
617
perfusion, and end-organ damage (Behl,
Hendrickson, and Moynihan, 2010). IgA and
IgG proteins can be overproduced in multiple
myeloma; however, less than 7% of patients
with
newly
diagnosed
myeloma
have
hyperviscosity (Kyle et al., 2003).
There is no relationship between the amount of
serum viscosity and the severity of clinical
symptoms (Behl, Hendrickson, and Moynihan,
2010). The normal range for serum viscosity is
1.2–2.8 centipoise (cP). It is unusual to see
clinical symptoms with serum viscosities less
than 3 cP. In patients with WM, one-third of
patients with a serum viscosity of 4 cP or
greater will be asymptomatic. Symptoms are
seldom seen in patients with IgM levels less
than 4 g/l; however, some patients will develop
symptoms with IgM levels between 3 and 4 g/l
(Halfdanarson, Hogan, and Moynihan, 2006;
Mullen and Wang, 2007).
Monitoring elements
The classic triad of symptoms in HVS includes
visual changes, neurologic changes, and
bleeding (Mullen and Wang, 2007). The onset
of symptoms is usually gradual (Halfdanarson,
Hogan, and Moynihan, 2006). Neurologic
changes may include headache, confusion,
vertigo, ataxia, and paresthesias. Visual changes
result from vascular changes in the retina. A
fundoscopic exam should be performed in all
patients with suspected HVS and will reveal
618
dilated, engorged veins referred to as “
‘sausage-like’ hemorrhagic retinal veins which
are pathognomic” for HVS (Higdon and
Higdon, 2006, p. 1877). This is a condition
known as fundus paraproteinaemicus. If
untreated, this leads to retinal vein occlusion
and “flame-shaped” hemorrhages (Behl,
Hendrickson, and Moynihan, 2010, p. 197).
Clinically, the patient may report blurred
vision, decreased visual acuity, and blindness if
left untreated. Mucosal bleeding of the gingiva,
nasal mucosa, gastrointestinal tract, or uterus
may result as the proteins coat the platelets and
interfere
with
clot
formation.
Other
life-threatening consequences of HVS include
congestive heart failure, acute tubular necrosis,
pulmonary edema, and multiorgan system
failure. A thorough assessment for signs and
symptoms of bleeding, as well as changes in
neurologic, cardiac, renal and visual function,
should be performed every 8 h.
Lab parameters including electrolytes, serum
viscosity, and quantitative immunoglobulin
measures should be monitored at least once
daily. Hyponatremia and hypercalcemia may be
seen. Hyponatremia is a false value due to
artifact from hyperproteinemia and does not
require interventions to correct hyponatremia.
Management
Plasmapheresis is the fastest way to decrease
plasma viscosity, especially in cases of elevated
619
IgM because most of the IgM is intravascular
(Halfdanarson, Hogan, and Moynihan, 2006).
In WM, a single pheresis session can effectively
decrease the serum viscosity and improve
symptoms. Conversely, in cases of IgA- or
IgG-associated HVS, multiple pheresis sessions
may be required to achieve the same results. In
centers where plasmapheresis is not available,
phlebotomy of 100–200 ml of whole blood has
demonstrated efficacy in improving symptoms
acutely.
Hydration with normal saline until euvolemia
or hypervolemia is achieved followed by loop
diuretics may also reduce serum viscosity.
Definitive treatment of hyperviscosity must
involve treatment of the underlying disorder,
usually with chemotherapy agents. Blood
transfusions for anemia must be used
judiciously and avoided if possible during
periods of hyperviscosity as packed RBCs can
increase serum viscosity and lead to
life-threatening vascular alterations (Behl,
Hendrickson, and Moynihan, 2010).
Hyperleukocytosis and leukostasis
Physiologic guidelines
Hyperleukocytosis is defined as a WBC count of
100 000/μl or more. Leukostasis is a result of
high WBC counts, contributing to increased
viscosity. Hyperleukocytosis with leukostasis is
seen in acute leukemias, including ALL with
620
11q23 translocations and AML subtypes M3,
M4, and M5. Up to 30% of adult AMLs can
present with hyperleukocytosis. Symptomatic
leukocytosis is more common in AML versus
ALL (Halfdanarson, Hogan, and Moynihan,
2006). A high WBC count is a negative
prognostic indicator. In ALL, patients who
present with a WBC greater than 30 000/μl
have a poorer prognosis (Hoelzer et al., 1988).
Symptomatic leukostasis is rarely seen in
chronic myelogenous leukemias and chronic
lymphoid leukemias even in the presence of
very high WBC counts (Halfdanarson, Hogan,
and Moynihan, 2006).
Increases in circulating leukocytes can increase
serum viscosity, resulting in sludging and
decreased perfusion in the microvasculature.
This is called leukostasis. Leukemic blasts also
interact with the vascular endothelial cells with
enhanced aggregation of blasts. There may also
be increased expression of adhesion molecules
on lymphoblasts and myeloblasts, increasing
the incidence of leukostasis.
Monitoring elements
The presentation of leukemic patients with
leukostasis is similar to patients with HVS.
Most commonly, the presenting symptoms are
respiratory
and
neurologic.
Pulmonary
symptoms include dyspnea on exertion or at
rest, chest pain, decreased oxygen saturation,
and tachypnea. Arterial blood gases may not be
621
helpful as pseudohypoxia can be seen due to
rapid consumption of plasma oxygen from large
numbers of leukocytes. A chest X-ray should be
performed to evaluate respiratory symptoms.
Findings can vary from normal to diffuse
infiltrates.
Neurologic manifestations can range from mild
confusion to somnolence. Focal neurologic
deficits can be seen and intracranial
hemorrhage must be ruled out. Other
symptoms can include visual changes due to
retinal hemorrhage or thrombosis, myocardial
infarction,
limb
ischemia,
renal
vein
thrombosis, and DIC. Fevers are also common
and may be high. The combination of
pulmonary symptoms and fever presents a
challenge as it may be difficult to distinguish
from infection. Infection should always be ruled
out and usually requires empiric management.
There are no specific tests to diagnose
leukostasis. The diagnosis is based on the WBC
count correlated with clinical symptoms.
Management
Reduction of the WBC count can be achieved
quickly with leukopheresis. There are no
evidence-based guidelines for the initiation of
leukopheresis. A blast count greater than 100
000/μl with clinical symptoms is an
appropriate finding to initiate decision making.
In AML, the goal is to reduce the WBC count to
less than 50 000/μl. In ALL, leukopheresis is
622
usually not necessary unless the blast count is
over 200 000/μl (Behl, Hendrickson, and
Moynihan, 2010).
Supportive measures include aggressive IV
hydration and careful monitoring of fluid
balance with strict input/output (I/O)
documentation. Transfusions must be avoided
unless critical as transfusions will further
increase viscosity and worsen symptoms. The
key to decreasing the WBC is initiation of
effective therapy. For myeloid leukemias,
hydroxyurea is initiated in a dosage of
50–100 mg/kg/day to provide cytoreduction
until chemotherapy can be initiated. Patients
with high WBC are at very high risk for tumor
lysis and must be managed accordingly (see
Section “Tumor lysis syndrome”). Cranial
radiation is rarely considered in patients with
acute mental status changes although there is
no good evidence to support this practice
(Halfdanarson, Hogan, and Moynihan, 2006).
Tumor lysis syndrome
Physiologic guidelines
Tumor
lysis
syndrome
(TLS)
is
a
life-threatening metabolic emergency that can
occur
spontaneously,
in
response
to
chemotherapy, or, less frequently, radiation
(Cortes et al., 2010). Tumor lysis results from
the massive release of intracellular contents
from tumor cells into the bloodstream as the
623
cells die. Intracellular anions (phosphate),
cations (potassium), and nucleic acids (uric
acid) are released into circulation in high
volumes resulting in hyperphosphatemia,
hyperkalemia, and hyperuricemia (Benoit and
Hoste, 2010). Phosphorous binds to calcium
resulting in hypocalcemia. The rapid, massive
release of electrolytes into the bloodstream
overwhelms and exceeds the ability of the
kidneys to filter and excrete (Varon and Acosta,
2010). Calcium–phosphate and uric acid
crystals can deposit in the renal tubules, leading
to acute kidney injury (AKI). TLS is a common
cause of AKI in critically ill patients (Benoit and
Hoste, 2010; Darmon et al., 2007). Other
sequelae of acute electrolyte imbalances include
heart failure, cardiac arrhythmias, pulmonary
edema, seizures, and death (Abu-Alfa and
Younes, 2010).
Risk categories can be divided into low,
intermediate, and high. High-risk factors
include patients with aggressive forms of
lymphoma
including
Burkitt’s
and
lymphoblastic lymphomas; acute lymphoblastic
leukemia (ALL), ALL with a WBC count greater
than or equal to 100 000/μl, or acute myeloid
leukemia with WBC ≥ 50 000/μl. The
intermediate risk category includes diffuse large
B cell lymphoma, ALL with WBC count 50
000–100
000/μl,
chronic
lymphocytic
leukemia with WBC count 10 000–100 000/μl
treated with fludarabine, or any other highly
624
chemosensitive tumor. Low-risk factors include
other non-Hodgkin’s lymphoma types and
other cancers with low growth rates (Coiffer et
al., 2008). Other risk factors for tumor lysis
include high LDH (>2× upper limit of normal),
preexisting renal disease, dehydration, sepsis,
and use of other nephrotoxic agents (Abu-Alfa
and Younes, 2010; Mughal et al., 2010).
Monitoring
The first step in monitoring patients for TLS is
to identify patients at risk. Early recognition
can lead to improved outcomes (Kennedy and
Ajiboye, 2010). As previously mentioned,
patients with high tumor burden who receive
effective treatment are those most at risk. TLS
can develop within hours of initial treatment
and up to 7 days thereafter (Cairo and Bishop,
2004). A baseline complete blood count will
help identify the degree of risk based on WBC.
A baseline LDH, potassium, uric acid,
creatinine, phosphorous, and urinalysis will
help determine the need for interventions.
Laboratory monitoring should be performed at
baseline, prior to initiation of treatment, and
every 6–12 h depending on the patient’s
baseline uric acid and renal function. If the
patient has an elevated creatinine at baseline in
addition to other risk factors, such as elevated
WBC or elevated uric acid, electrolytes should
be checked as frequently as every 6 h for the
first 48–72 h of chemotherapy or anticancer
625
treatment. Lab results should be evaluated for
results in relation to normal as well as trends
(see Table 11.1 for laboratory definition of TLS).
Lab results should be correlated with the
patient’s clinical findings.
Table 11.1 Laboratory and clinical findings in
tumor lysis syndrome.
Adapted from Cairo and Bishop (2004). Cairo
and Bishop (2004).
Laboratory TLS: two or more of the following
values within 3 days prior to or 7 days after the
initiation of cancer treatment
Uric acid ≥ 8 mg/dl or 25% increase from
baseline
Potassium ≥ 6.5 mEq/l or 25% increase from
baseline
Phosphorous ≥ 4.5 mg/dl or 25% increase
from baseline
Calcium ≤ 7 mg/dl or 25% decrease from
baseline
Clinical TLS: laboratory TLS + one or more of
the following items:
Serum creatinine ≥ 1.5× upper limit of normal
adjusted for age
Cardiac arrhythmia or sudden death
Seizure
626
Commonly, the patient with TLS presents
without symptoms and the condition is detected
based on lab results. Signs and symptoms
develop as a result of electrolyte imbalance and
AKI (see Table 11.2) and can develop within
24–48 h of starting therapy, with the exception
of hyperkalemia, which can occur as early as 6 h
from the start of anticancer treatment (Holmes
Gobel, 2006). With hyperuricemia, symptoms
do not develop until uric acid levels exceed
10 mg/dl, resulting in fatigue, nausea, vomiting,
and flank pain. When uric acid levels exceed
20 mg/dl, the patient may exhibit signs of renal
failure including oliguria, anuria, hypertension,
and edema (Lydon, 2005). Symptoms related to
elevated phosphate are usually a manifestation
of impaired renal function (Holmes Gobel,
2006). The nurse should assess for signs of
renal dysfunction such as oliguria but also must
assess for signs and symptoms of hypocalcemia.
Serum potassium levels exceeding 6.5 mEq/l
may
have
cardiac
sequelae
including
tachycardia, P and T wave changes, ventricular
tachycardia, and ventricular fibrillation.
Baseline and daily electrocardiograms (ECGs)
should be performed and repeated in the
setting of hyperkalemia. Patients with
potassium levels higher than 6 should be
monitored continuously for the development of
arrhythmias.
Table 11.2 Signs and symptoms of tumor lysis
syndrome.
627
Sources: Abu-Alfa and Younes (2010); Holmes
Gobel (2006); Kennedy and Ajiboye (2010).
Electrolyte
imbalance
Symptoms
Clinical
signs
Hyperkalemia
Lethargy
Weakness,
irritability
Syncope
Paresthesias
Muscle cramps
Nausea/
vomiting
Decreased
deep tendon
reflexes
Paralysis
Hyperactive
bowel sounds
Diarrhea
Cardiac
arrhythmias
Cardiac arrest
Early ECG
changes:
tachycardia,
prolonged QT
interval and ST
segment,
inversion of T
wave
Late ECG
changes:
bradycardia,
peaked T
waves,
depressed R
waves
progressing to
widened QRS,
628
Electrolyte
imbalance
Symptoms
Clinical
signs
prolonged PR,
loss of P wave;
ventricular
tachycardia,
ventricular
fibrillation,
heart block
Hyperuricemia
Lethargy
Fatigue
Weakness
Flank or back
pain
Malaise
Nausea,
vomiting
Pruritis
Hyperphosphatemia
Hypocalcemia
Hematuria
Gout (painful,
red, inflamed
joints)
Nephrolithiasis
Urate
nephropathy
Hypertension
Fluid volume
overload
Pulmonary and
peripheral
edema
Anuria
Oliguria
Azotemia
Edema
Hypertension
Acute renal
failure
Irritability/
restlessness
629
Carpopedal
spasm
Electrolyte
imbalance
Symptoms
Clinical
signs
Hallucinations,
confusion
Weakness
Depression,
anxiety
Twitching
Muscle cramps
Paresthesias
Tetany
Ventricular
arrhythmias
ECG changes
(prolonged QT
interval,
inverted T
waves; heart
block)
Facial
grimacing
Laryngeal
spasm
Psychosis
Intestinal
cramps
Chronic
malabsorption
Seizures
Respiratory
arrest
The nurse should thoroughly assess for signs
and symptoms of TLS including uremic
symptoms in patients with elevated creatinine
(mental status changes), fluid volume overload
unresponsive to diuretics, and severe acidosis.
Volume status must be evaluated regularly
including meticulous I/O measurements, often
requiring the use of indwelling urinary
630
catheters and checking daily weight. Daily
urinalysis for the presence of blood and crystals
should be performed. Patients with oliguria
must have a renal ultrasound performed to rule
out obstructive uropathy (Mughal et al., 2010).
Treatment
The mainstay of treatment is the recognition of
at-risk patients, prevention, and early
intervention. Prevention of TLS includes
vigorous IV hydration with judicious use of
diuretics if needed. Aggressive volume repletion
should be implemented immediately at the time
of presentation to minimize delays in initiation
of effective anticancer treatment. Expanding
plasma volume facilitates renal blood flow and
therefore urine flow, promoting excretion of
potassium, phosphate, and uric acid. Clearance
of uric acid crystals is directly dependent on the
glomerular filtration rate, so optimization of
renal blood flow is critical. The goal is to
maintain a urine output of 80–100 ml/m2/h.
This goal may not be realistic or safe in
individuals with congestive heart failure and
may necessitate the use of diuretics to achieve
the goal (Abu-Alfa and Younes, 2010). Diuretics
may only be used if the patient has been
hyperhydrated; the use of diuretics in patients
with hypovolemia or obstructive uropathy may
exacerbate renal insufficiency (Kennedy and
Ajiboye, 2010). Furthermore, use of diuretics
has not demonstrated improved outcomes such
631
as survival, or decreased the need for
hemodialysis (Karajala, Mansour, and Kellum,
2009).
Management of electrolyte
imbalances
Hyperkalemia
Review the patient’s medication list for other
medications that may increase serum
potassium levels including supplemental
potassium, angiotensin-converting enzyme
(ACE) inhibitors, direct rennin inhibitors,
aldosterone antagonists, potassium-sparing
diuretics (spironolactone), and nonsteroidal
anti-inflammatory drugs. A low potassium diet
should be implemented. Care should be used to
monitor for potassium amounts in dietary
supplements and enteral and parenteral
nutrition formulations (Holmes Gobel, 2006).
Medications to lower potassium levels should
be employed when the patient is symptomatic
or the potassium level is above normal. Sodium
polystyrene sulfonate resin (Kayexalate®) can
be employed (60 g orally or via retention
enema); however, this agent takes several hours
to take effect and should not be the sole or first
measure used in an acute setting. This agent
works by exchanging potassium for sodium in
the colon, resulting in potassium losses through
stool output. There is no strong evidence to
632
support the use of this agent in the acute setting
(Abu-Alfa
and
Younes,
2010).
Contraindications to Kayexalate use include
serum potassium less than 5 mmol/l, history of
hypersensitivity to polystyrene sulfonate resins,
and obstructive bowel disease (Kayexalate
prescribing
information,
2010).
Contraindications to enema use include low
platelet count and neutropenia. Loop diuretics
such as furosemide lower potassium quickly by
enhancing urinary excretion. These agents will
also help to prevent fluid volume overload due
to hyperhydration. Regular human insulin (10
units) and glucose (50 ml of 50% solution)
administered intravenously also work to lower
potassium. The insulin load results in shifting
of potassium from the extracellular space back
into the cell. Glucose is administered
concominantly to avoid hypoglycemia. This
intervention works within 20 min and lasts as
long as 6 h. Inhaled beta agonists (10–20 mg of
nebulized albuterol) may also be given to lower
serum potassium, acting in a similar fashion to
insulin, driving potassium back into the cell.
Calcium gluconate 10 ml of 10% solution (1 g)
IV over 5–10 min is often administered
intravenously in patients with symptomatic
hyperkalemia.
The
calcium
temporarily
antagonizes the cardiac effects of hyperkalemia,
stabilizing the cardiac membrane. The calcium
has an onset of 1–3 min and lasts up to 1 h.
Sodium bicarbonate (50 mEq IV over
5–10 min) causes a temporary shift of
633
potassium into the cells in the setting of
acidosis. The effects and duration of action are
variable (Mughal et al., 2010). Refractory and
symptomatic hyperkalemia may require
hemodialysis.
Hyperphosphatemia with secondary
hypocalcemia
High levels of phosphate in the blood are
primarily managed with the administration of
oral phosphate binding agents, forced diuresis,
and dietary restriction of phosphorous. If
possible, avoid providing calcium replacement
(unless
the
patient
has
symptomatic
hypocalcemia) as any supplemental calcium will
increase
the
opportunity
for
phosphorous–calcium precipitation (Abu-Alfa
and Younes, 2010). Patients with serum
calcium levels less than 8 mg/dl should be
placed on seizure precautions (Holmes Gobel,
2006).
Hyperuricemia
Aggressive IV hydration to promote urine
output of 80–100 ml/m2/h is the goal to
maintain urinary excretion of excess uric acid.
Uric acid becomes more soluble in an alkaline
environment. However, urinary alkalinization is
controversial
because
calcium–phosphate
crystals are more soluble in an acidic urine
environment. Therefore, urinary alkalinization
634
may lead to increased calcium–phosphate
crystallization. In the past, the addition of
sodium bicarbonate to IV fluids was a mainstay
of practice in order to achieve an alkine urine
pH. However, this practice is no longer
recommended due to lack of strong data to
support safety and efficacy (Kennedy and
Ajiboye, 2010; Mughal et al., 2010). Hydration
using an isotonic solution such as normal saline
is recommended.
Use of medications to prevent and manage
hyperuricemia is critical. Allopurinol is a
xanthine oxidase inhibitor that inhibits the
conversion of hypoxanthine to xanthine and
xanthine to uric acid, resulting in the
accumulation of these precursors and
preventing the accumulation of uric acid.
Xanthine and hypoxanthine are substances that
are 5–10 times more soluble in urine than uric
acid. Allopurinol must be instituted early,
before elevations in uric acid occur, in order to
effectively mitigate the risk of hyperuricemia.
As described earlier, allopurinol changes
nucleic acid metabolism but cannot metabolize
uric acid that has already accumulated.
Allopurinol is available in oral and IV
formulations. Allopurinol should be started
24–48 h prior to the start of anticancer therapy.
Recommended daily dosing of IV allopurinol is
200–400 mg/m2 or 600–800 mg/day in
divided doses for oral allopurinol. Allopurinol
635
must be dose-adjusted for renal dysfunction.
Side effects include rash, hypersensitivity
reactions, and renal lithiasis secondary to
xanthine accumulation (Abu-Alfa and Younes,
2010). If a rash develops in a patient receiving
allopurinol, it must be discontinued as severe
cutaneous reactions have been reported.
Allopurinol interferes with the cytochrome
p450 system and will interact with other drugs
with similar activity (Kennedy and Ajiboye,
2010).
Febuxostat is a newer xanthine oxidase
inhibitor that is more effective than allopurinol
in treating hyperuricemia (Becker et al., 2005).
The daily dose is 120 mg, taken orally. The drug
does not require dose adjustments for renal
insufficiency. Side effects include liver function
abnormalities, nausea, arthralgia, and rash
(Uloric® prescribing information, 2009).
Rasburicase is an enzyme that breaks uric acid
down into allantoin, a substance 5–10 times
more soluble than uric acid. Rasburicase is
Food and Drug Administration (FDA)-approved
for the prevention and management of
hyperuricemia in adults and children with
cancer at a dose of 0.20 mg/kg IV over 30 min
as a single daily dose for up to 5 days (Elitek®
package insert). Rasburicase provides control of
uric acid levels more rapidly than allopurinol
(Cortes et al., 2010). Other benefits to
rasburicase include lack of drug interactions
636
and no requirements for dose adjustments in
renal dysfunction (Kennedy and Ajiboye, 2010).
Contraindications to rasburicase use include
G6PD deficiency, pregnancy, and breastfeeding
(Abu-Alfa and Younes, 2010). Studies have
examined the efficacy and different dosing
schedules for rasburicase (Campara, Shord, and
Haaf, 2009; Hummel et al., 2008a; Hutcherson
et al., 2006; Kennedy and Ajiboye, 2010; Lee et
al., 2003; Liu, Sims-Mccallum, and Schiffer,
2005; Malaguarnera et al., 2009; McDonell et
al., 2006; Reeves and Bestul, 2008; Trifilio et
al., 2006). Hummel et al. (2008a)
demonstrated that a lower dose (0.04 mg/kg)
for 1–2 doses is effective. Other researchers
have looked at fixed dosing schedules ranging
from 3 to 9 mg/dose (Campara, Shord, and
Haaf, 2009; Malaguarnera et al., 2009;
McDonell et al., 2006; Reeves and Bestul,
2008). Giraldez and Puto (2010) performed a
retrospective study examining a 6 mg fixed dose
in 15 patients with TLS. This single dose
effectively reduced uric acid levels. In practice,
the lowest effective dose in the fewest doses
necessary to lower uric acid to below normal
should be employed. Many centers are now
using 6 mg fixed-dosing schedules and
repeating the dose after 24 h if needed. Side
effects of rasburicase include hypersensitivity
reactions, hemolysis, and methemoglobinemia
if given to patients with G6PD deficiency, and
rash (Kennedy and Ajiboye, 2010).
637
There are no large-scale randomized controlled
trials comparing rasburicase dose and
frequency or absolute threshold levels for
rasburicase use. Additionally, there are no data
on the impact of rasburicase on outcomes
including AKI, renal failure, hemodialysis use,
or mortality (Kennedy and Ajiboye, 2010).
Acute kidney injury
In the event of AKI in the patient with
impending or actual TLS, a nephrology consult
should be placed. The goals are to minimize
delays in anticancer therapy and optimize renal
function. The tenets of AKI management
include managing volume status, correcting
electrolyte
abnormalities,
avoiding
nephrotoxins, and adjusting medications for
renal function (Abu-Alfa and Younes, 2010).
The development of AKI may exacerbate
preexisting
electrolyte
abnormalities,
particularly hyperkalemia and hyperuricemia
(Benoit and Hoste, 2010). Hemodialysis or
renal replacement therapy may be considered
in patients with large tumor burden, elevated
WBC count, chronic kidney disease, end-stage
renal disease, or AKI at the time of
presentation, or congestive heart failure. Other
authors have suggested that renal replacement
therapy be employed when hyperphosphatemia
continues for more than 6 h after the initiation
of vigorous hydration (Darmon, Roumier, and
Azoulay, 2009). The use of hemodialysis in this
638
setting is not well studied and cannot be
routinely recommended.
Suggested criteria for hemodialysis include the
following parameters unresponsive to other
measures (Mughal et al., 2010; Varon and
Acosta, 2010):
Potassium ≥ 6 mEq/l
Uric acid ≥ 10 mg/dl
Phosphorous ≥ 10 mg/dl
Fluid volume overload unresponsive to
diuretics
Symptomatic hypocalcemia
Severe acidosis
Uremic symptoms such as mental status
changes
Evidence-based treatment guidelines
In 2008, evidence-based guidelines for the
prevention and treatment of TLS in adults and
children were published (Coiffer et al., 2008).
The guidelines are the first to outline specific
roles for both allopurinol and rasburicase
(Mughal et al., 2010). An algorithm based on
TLS risk was developed. For low-risk patients,
no
interventions
for
prevention
are
recommended. For intermediate-risk patients,
hydration and allopurinol are recommended as
initial therapy to prevent hyperuricemia.
Allopurinol should start 12 h prior to anticancer
639
therapy and continue until the patient is
considered to be at low risk. If hyperuricemia
develops with these interventions in place,
rasburicase should be instituted. For high-risk
patients, hydration and rasburicase use upfront
is recommended (Coiffer et al., 2008).
Clinical Pearls
Blood samples for patients who have received
rasburicase must be sent to the lab on ice.
Failure to do so results in falsely low levels of
uric acid as rasburicase will continue to break
down uric acid in the blood sample if not
chilled (Abu-Alfa and Younes, 2010; Elitek
package insert).
Structural emergencies
Traditional oncologic emergencies such as
superior vena cava syndrome and spinal cord
compression rarely require transfer to intensive
care settings. Improvements in preventive
strategies and improved diagnostic techniques
have transferred the management of these
conditions to oncology or medical surgical units
(Demshar, Vanek, and Mazanec, 2011).
However, patients at risk for these conditions
may require intensive care for other diseases or
treatment-related complications. Therefore, the
critical care advanced practice registered nurse
640
should be aware of signs and symptoms of
impending structural emergencies, including
superior vena cava syndrome and spinal cord
compression. Presenting signs and symptoms,
diagnostic techniques, and management
strategies for each are outlined in Table 11.3.
Table 11.3 Traditional oncologic emergencies.
Sources: Behl, Hendrickson, and Moynihan
(2010); Demshar, Vanek, and Mazanec (2011);
Halfdanarson, Hogan, and Moynihan (2006);
Higdon and Higdon (2006); Kaplan (2006).
Emergency
Signs and
symptoms
Diagnosis
Hypercalcemia Vague and
Corrected serum
nonspecific
calcium > 10.5 mg/dl
Confusion,
lethargy
Nausea,
vomiting,
constipation,
abdominal
pain
Polyuria,
elevated
creatinine
Shortened QT
interval on
ECG,
arrhythmias
641
Mana
Hydra
norma
rates b
200 a
300 m
contra
by
cardio
status
Once v
replet
diuret
used t
calciu
excret
Bispos
therap
Emergency
Signs and
symptoms
Diagnosis
Mana
pamid
(60–9
cautio
dysfun
zoledr
(4 mg
for ren
dysfun
Calcit
fast ef
has sh
durati
leads
tachyp
Steroi
useful
selecte
Vitam
D3–in
hyper
Syndrome of
inappropriate
antidiuretic
hormone
Fatigue
Difficulty
concentrating
Poor memory
Headache
Muscle
cramps
Dysgeusia
In cases of
642
Serum
osmolality < 275 mOsm/
kg in a euvolemic
patient
Urine
osmolaltiy > 100 mOsm/
kg
FENa > 1%
Treat
cause
Fluid
of 0.5–
water
Increa
intake
If sym
severe
Emergency
Signs and
symptoms
Diagnosis
severe
hyponatremia:
Confusion
Hallucinations
Seizures
Coma
Superior vena Upper body
cava syndrome edema
Dyspnea,
stridor
Dysphagia
Superficial
venous
dilatation
Headaches
Confusion
643
Mana
saline
intrav
with c
Be car
correc
too qu
result
pontin
myelin
Correc
sodium
quickl
8–10 m
24 h
Furos
contra
with 3
CT scan
Plain radiography
Venography
Treat
malign
Emerg
situati
(prese
CNS
sympt
Stent
radiat
therap
cortico
diuret
Emergency
Signs and
symptoms
Diagnosis
Mana
Elevat
bed
Suppl
oxyge
Malignant
spinal cord
compression
Back pain
MRI
Radicular pain
Motor
weakness
Gait
disturbance
Bowel and
bladder
dysfunction
Cardiac tamponade
Physiologic guidelines
Cardiac tamponade is a life-threatening
oncologic emergency that results from excessive
fluid accumulation in the pericardium. The
fluid accumulation is referred to as a pericardial
effusion and precedes tamponade. Excess fluid
exerts pressure on the cardiac chambers,
restricting the filling capacity of the ventricles.
The end result is decreased cardiac output and
hemodynamic instability (Turner Story, 2006).
Tamponade can occur with fluid volumes as
little as 50–80 ml and as much as 2 l (Behl,
644
Gluco
(Dexa
initial
10–16
follow
4 mg e
4–6 h
Radia
therap
Surge
Hendrickson, and Moynihan, 2010; Turner
Story, 2006).
Patients with cancer can develop pericardial
effusions as a result of tumor cell invasion into
the pericardial fluid, as a side effect of
anticancer treatment, or as a result of tumor
extension into the pericardial space (Behl,
Hendrickson,
and
Moynihan,
2010).
Mesothelioma is the most common primary
tumor type that involves the pericardium and is
a difficult disease to treat. Other primary
tumors of the heart include malignant fibrous
histiocytoma,
rhambdomyosarcoma,
and
angiosarcoma (Turner Story, 2006). Most
effusions develop from lung or breast cancer;
other causes include melanoma, leukemia, or
lymphoma (Higdon and Higdon, 2006). Tumor
obstruction of mediastinal lymph nodes can
interfere with lymph drainage from the
pericardium, leading to fluid accumulation.
This is the most common cause of pericardial
effusion in malignancy. Malignant effusions
progress to tamponade more often than
nonmalignant effusions because the presence of
tumor cells stimulates the pericardium to
produce excessive fluid (Turner Story, 2006).
Tumors may also cause bleeding in the
pericardial space, allowing rapid accumulation
of fluid and increasing the risk for tamponade
(Flounders, 2003). Many patients have
metastatic disease in other sites at the time of
presentation with pericardial effusion; the
645
mean interval from diagnosis to development of
tamponade is 17.4 months (Cozzi et al., 2010).
Radiation therapy with doses of 4000 cGy or
more to the chest is associated with the
development of pericardial effusions. The
majority of cases occur in the first year after
radiation therapy (Miaskowski, 1999).
Chemotherapy and biotherapy agents can also
cause pericardial effusions. Other conditions
that may increase risk include underlying heart
disease,
systemic
lupus
erythematosus,
rheumatoid arthritis, scleroderma, myxedema,
tuberculosis, bacterial endocarditis, and
pericarditis (Turner Story, 2006).
Pericardial effusions are classified by fluid type.
Transudative fluids are low in protein and are
the result of abnormal capillary permeability
caused by benign mechanical factors such as
cirrhosis. Transudative fluid is defined as
having LDH levels less than 200 IU/l and
protein levels less than 35 g/dl. Exudative
effusions are protein-rich and are caused by
leaking blood vessels due to increased capillary
permeability. Exudative fluid has LDH levels
greater than 200 IU/l and protein levels greater
than 35 g/dl. Most malignant pericardial
effusions are exudates.
Monitoring
Identification of tamponade is critical as
unrecognized, untreated tamponade has a
646
mortality rate of 65% (Miaskowski, 1999). The
presence and severity of symptoms depend on
how quickly the fluid has accumulated. The
classic Beck triad of symptoms includes
distended neck veins, silent precordium, and
hypotension. These symptoms are rarely seen in
malignancy as fluid tends to accumulate slowly
over time (Behl, Hendrickson, and Moynihan,
2010; Schairer et al., 2011). Patients may report
dyspnea; dull, diffuse chest pain, or heaviness
that does not change with position;
palpitations; nonproductive cough; dizziness;
and fatigue (Higdon and Higdon, 2006).
Symptoms may be mistaken for right heart
failure and treated with diuretics. Diuretics will
further decrease cardiac output and worsen
hemodynamic instability; therefore, diuretics
should be avoided until the cause of the
symptoms is confirmed. As tamponade
progresses, dyspnea worsens and confusion
may ensue. Relief of symptoms may be achieved
by sitting up and leaning forward.
A thorough exam reveals distant or quiet heart
sounds, a narrow pulse pressure, and pulsus
paradoxus. Patients at risk for cardiac
tamponade should be placed on continuous
cardiac monitoring to assess for changes in
cardiac rhythm. Additionally, a 12-lead ECG
should be performed. ECG changes consistent
with tamponade include low-voltage complexes
with nonspecific ST-T changes. Electrical
alternans may be seen in patients with large
647
effusions or tamponade (Behl, Hendrickson,
and Moynihan, 2010; Lau et al., 2002). ECGs
assist in diagnosing tamponade and also guide
the need for interventions (see Fig. 11.2).
Figure 11.2 Electrical alternans in malignant
cardiac
tamponade.
Twelve-lead
electrocardiogram shows electrical alternans.
Note the alternating amplitude and vector of
the P waves, QRS complexes, and T waves.
Reprinted with permission from Lau et al.
(2002). Cardiac Tamponade and Electrical
Alternans, Texas Heart Institute Journal.,29.
66–67. Copyright 2002 by the Texas Heart
Institute”.
Management
Successful treatment of pericardial effusion in
patients with cancer may improve both quality
and quantity of life (Cozzi et al., 2010). There is
no “gold standard” for the management of
malignant pericardial effusion and treatment
decisions must be individualized to the patient.
648
Options for patients with malignant pericardial
effusion
include
pericardial
sclerosing,
pericardial
window,
radiotherapy,
and
intrapericardial instillation of cystostatic agents
(Maisch, Ristic, and Pankuweit, 2010). In
patients with cancer, invasive strategies may be
contraindicated by coagulopathies or coexisting
cytopenias. Platelet transfusions can be used to
increase the platelet count to an acceptable
level (generally above 50 000). Cozzi et al.
(2010) described a case series of seven patients
with malignant effusions treated with
pericardiocentesis. Patients tolerated the
procedure well with no cardiovascular
complications. Symptoms resolved rapidly and
there were no cases of recurrence at 30 days.
However, most cases of pericardial effusion will
recur if further definitive therapy is not
instituted (Cozzi et al., 2010).
For chemosensitive tumors, management of the
underlying disease is essential. Systemic
chemotherapy may be helpful. Intrapericardial
installation of chemotherapy has been used in
an attempt to sclerose the pericardial space to
prevent fluid reaccumulation. Agents including
bleomycin,
carboplatin,
cisplatin,
and
mitomycin-C have been used for this purpose
(Kaira et al., 2005; Maisch, Ristic, and
Pankuweit, 2010; Maruyama et al., 2007;
Moriya et al., 2000). Sclerosis is safe and
effective with minimal systemic side effects.
649
Randomized, case–control studies are needed
to assess the best management strategies for
malignant pericardial effusion. However,
aggressive
management
of
malignant
pericardial effusion may result in improved
quality of life and improved life expectancy,
with minimal toxicity (Cozzi et al., 2010).
Malignant airway obstruction
Physiologic guidelines
Obstructions in the airway can be caused by
intrinsic
tumors
growing
inside
the
tracheobronchial tree, or by compression or
extension into the airway by extrinsic tumors
(Chan,
2011).
Primary
bronchogenic
carcinomas including small cell and non-small
cell lung cancers that cause extrinsic
compression are the most common cause of
malignant
airway
obstruction
(Behl,
Hendrickson, and Moynihan, 2010; Chan,
2011). Primary intrinsic tumors of the trachea
and bronchi are rare (Chan, 2011). Other
primary cancers such as thyroid, esophageal,
and lymphadenopathy from lymphoma can
result in airway obstruction. The incidence of
malignant central airway obstruction is 80
000/year (Chen, Varon, and Wenker, 1998).
Approximately 35–40% of patients die from
complications, and early intervention can
improve quality of life and extend survival
(Chan, 2011).
650
Central
airway
obstruction
may
be
misdiagnosed as asmtha or chronic obstructive
pulmonary disease (COPD). To distinguish
between central airway obstruction and asthma,
administration of inhaled bronchodilators or
steroids can aid in the diagnosis. Patients with
central airway obstruction will not improve
with administration of these agents (Chen,
Varon, and Wenker, 1998).
Monitoring
The severity of symptoms depends on the size
and location of the tumor as well as the rate of
tumor growth (Chan, 2011). Symptoms may
have a gradual onset if the tumor is
slow-growing or may present acutely in rapidly
growing tumors. Dyspnea and hemoptysis are
the most common presenting symptoms (Chen,
Varon, and Wenker, 1998). Symptoms worsen
in the supine position. In severe cases, the
supine position can decrease right ventricular
output, causing cardiac arrest (Chen, Varon,
and Wenker, 1998). Early symptoms may
include dyspnea and tachycardia. Later
symptoms may include stridor, cough,
hemoptysis,
anxiety,
impending
doom,
increased work of breathing, and diaphoresis
(Chan, 2011). Physical exam may reveal
decreased or absent breath sounds, stridor,
wheezing, or use of accessory muscles. Chest
excursion may be asymmetric; palpation of the
chest wall may reveal decreased tactile fremitus
651
over the involved area. Percussion of the
involved area reveals dullness (Chen, Varon,
and Wenker, 1998). Assess the skin for pallor,
cyanosis, and diaphoresis. Assess the heart rate;
bradycardia, perioral or acral cyanosis, and
obtundation signal severe airway compromise
(Chan, 2011; Chen, Varon, and Wenker, 1998).
Pneumonia is a common sequela of central
airway obstruction; therefore, patients may also
exhibit signs and symptoms of respiratory
infection. Patients at risk for impending airway
obstruction should be monitored via continuous
oxygen saturation to assess the severity of
hypoxemia.
Chest radiographs may be done in acute
situations to rule out other causes of hypoxia
including
pneumothorax
(Chan,
2011).
Computed tomography (CT) is preferred over
chest radiograph to evaluate tumor size, depth
of invasion, and extent of obstruction (Chan,
2011). Bronchoscopy is also helpful in direct
visualization of the airway and is considered the
gold standard for evaluating central airway
obstruction (Chan, 2011). Bronchoscopy allows
visualization of the tumor, facilitates distinction
between intrinsic and extrinsic obstruction, and
allows the opportunity for tissue biopsy (Chan,
2011). Bronchoscopy also provides an
opportunity for therapeutic intervention.
652
Management
Before embarking on an intervention for airway
obstruction,
consider
the
patient’s
comorbidities, hemodynamic stability, cancer
type, overall prognosis, and availability of
technology (Chan, 2011). A patient with a poor
overall prognosis may still benefit from
intervention in order to improve quality of life;
however, less invasive strategies may be
considered.
The most important intervention is to establish
and maintain a patent airway (Behl,
Hendrickson, and Moynihan, 2010). Patients
with impending airway obstruction must have
suction supplies set up at the bedside as well as
intubation supplies with endotracheal tubes of
different sizes, and a tracheostomy kit with a
variety of tube sizes in case of emergent
tracheotomy. Use of supplemental oxygen,
nebulized bronchodilators, and IV steroids may
help stabilize the patient and improve
symptoms while a plan is developed (Chen,
Varon, and Wenker, 1998). Intubation may be
difficult and technique is selected based on the
level of airway obstruction. Lesions in the upper
airway may require a tracheostomy while
lesions in the lower airway will require
endotracheal intubation that allows the end of
the tube to lie beyond the obstruction (Chen,
Varon, and Wenker, 1998). Some tumor types
653
are highly vascular and bleeding is a potential
complication.
Maintaining spontaneous ventilation is a
priority in patients with central airway
obstruction. Strategies to maintain spontaneous
ventilation include avoidance of agents that
cause respiratory depression including opioids
and muscle relaxants, avoidance of general
anesthesia, and positive pressure ventilation
(Chen, Varon, and Wenker, 1998). If sedatives
are required, use of medications that do not
suppress respirations, such as haldol, should be
used (Chen, Varon, and Wenker, 1998). Avoid
the supine position as it may exacerbate
symptoms and result in decreased right
ventricular output (Chen, Varon, and Wenker,
1998). Acceptable position changes include
sitting, decubitus, and prone (Chen, Varon, and
Wenker, 1998).
Use of helium–oxygen combinations (80%
helium, 20% oxygen) have been used
successfully in the management of patients with
central airway obstruction (Curtis et al., 1986;
Mizrahi
et
al.,
1986;
Orr,
1988).
Helium–oxygen concentrations have an
increased density, resulting in decreased work
of breathing and therefore decreased energy
requirements (Boorstein et al., 1989).
Improvements in work of breathing should be
seen within minutes of initiation of
helium–oxygen therapy (Boorstein et al., 1989).
654
Therapeutic interventions for malignant central
airway obstruction include bronchoscopy,
balloon
bronchoplasty,
laser
resection,
argon-plasma
electrocoagulation,
stent
insertion, surgical resection, and radiation
therapy. Bronchoscopy involves the use of a
rigid bronchoscope with a wide diameter to
visualize and treat tumors while allowing
ventilation (Chan, 2011). The sharp tip of the
bronchoscope may be used to debulk the tumor
and apply pressure to facilitate hemostasis.
Risks include damaging healthy tissue and
perforating the mediastinum (Chan, 2011). Use
of a rigid bronchoscope requires sedation and
can only be used in patients with enough
respiratory capacity to safely tolerate sedation
(Chan, 2011). Balloon bronchoplasty uses a
balloon to dilate the compromised airway.
Advantages are that the results are immediate
and can be used for intrinsic or extrinsic
compromise. Disadvantages include temporary
effects and the need for additional
interventions.
Complications
include
pneumothorax, mediastinitis, and bleeding
(Chan, 2011).
Laser resection uses Neodynium:yttrium
aluminum garnet (Nd:YAG) laser to transmit
light energy to tissue. Laser therapy is delivered
using either a flexible or rigid bronchoscope.
The thermal energy is absorbed by the tumor
tissue and the blood vessels supplying the
tumor. This results in devascularization of the
655
tumor as well as vaporization of the tumor. The
primary risk is damage to healthy surrounding
tissue (Chan, 2011). Other complications
include bleeding, hypoxemia, tracheobronchial
perforation, infection, pneumothorax, fistula,
and endobronchial burns (Han, Prasetyo, and
Wright, 2007; Stanopoulos et al., 1993). While
this modality is successful in demonstrating
76% decrease in dyspnea and 94% rate of
hemoptysis management, the relief is
temporary (Han, Prasetyo, and Wright, 2007).
Laser therapy is most successful in cases of
acute obstruction, partial obstruction, intrinsic
obstruction without cartilage involvement,
growth less than 4 cm axially, tumor visible
through bronchoscope, and healthy lung tissue
distal to obstruction (McElvein and Zorn,
1984). Laser therapy may not be appropriate in
cases of highly vascular tumors, widespread
metastatic disease, or aggressive tumor types
(Gillis et al., 1983).
Argon-plasma electrocoagulation uses a probe
with a spark at the end, with argon gas released
at the tip, causing an ionized plasma that causes
“coagulative necrosis” at the tumor site (Chan,
2011, p. 8). Argon-plasma electrocoagulation
can treat tumors that may not be accessible by
laser therapy. The disadvantage is that
argon-plasma electrocoagulation does not
penetrate tissue as deeply as laser energy. This
mode may be preferable for superficial tumors
(Chan, 2011).
656
Stents made of silicone, metal, or a combination
of both may be used to relieve obstruction in
patients with extrinsic tumor compression or
tracheoesophogeal fistula. While stenting does
not improve survival, it does significantly
improve symptoms (Wood et al., 2003).
Benefits include restoration of airway patency,
improved ventilation, and facilitation of
secretion clearance (Chan, 2011). Complications
include stent migration, stent obstruction,
granulation tissue growth, and perforation.
External beam radiation therapy (EBRT) is the
preferred treatment modality to decrease tumor
size and provide palliation (Chan, 2011; Chen,
Varon, and Wenker, 1998). Palliative doses of
EBRT for the treatment of airway obstruction
are 3000 cGy in 10 daily fractions. Side effects
include skin changes to the involved field and
fatigue. Patients must be monitored closely for
worsening of symptoms as radiation-induced
edema may results in worsening of obstructive
symptoms within the first few days of therapy
(Chen, Varon, and Wenker, 1998).
Brachytherapy, which involves placement of a
radioactive source directly at the tumor site, has
been shown to decrease symptoms and improve
quality of life. This mode is contraindicated
with tumors that invade major arteries (Chan,
2011). Side effects include bronchitis,
hemoptysis, bronchial stenosis, and bronchial
fistula (Chan, 2011).
657
Surgical resection is typically reserved for
patients with localized (i.e., nonmetastatic)
disease and is a potentially curative option
(Chan,
2011).
Surgical
resection
is
contraindicated
if
complete
resection
jeopardizes healing of the anastomosis, if the
tumor length exceeds 50% of the trachea, or if
vital structures such as the aorta are involved
(Chan, 2011).
Before any of these interventions are employed,
a discussion with the oncology team, the
patient, and family should take place to discuss
overall prognosis and goals of care. In patients
with a curative intent, more aggressive
interventions such as surgery followed by
adjuvant therapy may be most appropriate,
while patients with metastatic disease would
benefit from palliative interventions that will
improve quality of life and minimize suffering.
Carotid blowout syndrome
Physiologic guidelines
The clinical signs and symptoms of carotid
artery rupture are referred to as carotid blowout
syndrome (CBS; see Fig. 11.3) (Chang et al.,
2007). Carotid artery rupture occurs in 3–4% of
patients with head and neck cancer with a
mortality rate of 40–50% (Chaloupka et al.,
1999; Citardi et al., 1995; Garcia-Egido and
Payares-Herrera, 2011; Macdonald et al.,
2000). The common carotid artery arises from
658
the aorta on the left and the brachiocephalic
artery on the right. The carotid arteries supply
most of the blood to the head and neck. The
carotids bifurcate at the level of the hyoid bone
into internal and external branches. The
bifurcation point is the thinnest and most
vulnerable to rupture. The arteries have three
layers: adventitia (connective tissue), media
(smooth muscle), and intima (endothelial cells).
The adventitia provides protection for the
artery. The vasovasorium provides 80% of the
nutrition to the arterial wall. If nutrition is
interrupted by infection, ischemia, tumor
invasion, radiation, or surgical damage, the
arterial wall weakens, increasing the risk for
pseudoaneurysm and rupture (Lesage, 1986).
Radiation therapy creates free radicals, which
cause fibrosis and weakening of the adventitia
(Powitzky et al., 2010).
659
Figure 11.3
algorithm.
Carotid
blow-out
syndrome
Risk factors for CBS include radical neck
resection, radiation therapy and postradiation
necrosis, combined radio–surgery techniques,
recurrent tumor with soft tissue invasion,
infection, pharyngocutaneous fistula formation,
poor wound healing, and flap necrosis with
carotid exposure (Chaloupka et al., 1996; Chang
et al., 2007; Garcia-Egido and Payares-Herrera,
2011; Macdonald et al., 2000; Maran, Amin,
and Wilson, 1989). History of radiation therapy
is the most common risk factor and adds a
7.6-fold increase in the risk of carotid artery
blowout in patients with head and neck cancer
(Maran, Amin, and Wilson, 1989). Time from
diagnosis to development of CBS ranges from
660
as early as 6 months to 12 years, with an
average time of 2.7 years (Chang et al., 2007;
Powitzky et al., 2010).
There are three types of carotid artery rupture:
type I (threatened), type II (impending), and
type III (acute). In type I, there is exposure of
the carotid artery because of a wound, fistula,
or necrosis, or from neoplastic invasion of the
carotid
system
with
nonhemorrhagic
pseudoaneurysm (Chang et al., 2007; Powitzky
et al., 2010). Carotid artery rupture is inevitable
if tissue is not covered with healthy,
vascularized tissue. Type II carotid artery
rupture is classified by short episodes of acute
hemorrhage that resolve spontaneously or with
simple surgical packing or pressure (Chang et
al., 2007; Powitzky et al., 2010). Impending
rupture is almost certain to result in complete
rupture if there is no intervention. Type III
carotid artery rupture includes acute, profuse
hemorrhage that is not self-limiting or
controlled with surgical packing alone; there is
complete rupture of the vessel (Chang et al.,
2007). Carotid artery rupture may occur in the
internal carotid artery, the common carotid
artery, the external carotid artery, or at the
bifurcation.
Monitoring
CBS may occur without warning. At-risk
patients should be closely monitored for signs
and symptoms of impending rupture. Minor
661
bleeding from the wound, flap site,
tracheostomy, or mouth may signal slow tumor
erosion of the vessel; visible pulsation of the
artery, tracheostomy, or flap site; ballooning of
an artery; irritability or restlessness. CBS may
be instigated by increased pressure from
coughing, retching, vomiting, or straining.
CT scan or magnetic resonance imaging (MRI)
may be used to classify rupture type and
identify patients who may benefit from early
intervention. Angiography is the gold standard
for diagnosis but is associated with an 8.5%
complication rate (Powitzky et al., 2010). A
diagnostic grading system has been established
to help identify patients who may benefit from
early intervention. Grade 0 is no evidence of
carotid disruption; Grade 1 is focal weakening
or disruption of the vessel wall; Grade 2 is
development of pseudoaneurysm; Grade 3 is
extravasation from ruptured artery (Chang et
al., 2008). Ideally, intervention is initiated
prior to progression to Grade 3.
Following intervention for CBS, the patient
should be observed closely for neurologic
deficits, which are the most common
complications of CBS treatments (Lesage,
1986). Neurologic examination should include
level of responsiveness, posture and motor
activity, quality and size of pupils and reaction
to light, and speech quality (Lesage, 1986).
Neurologic sequelae of CBS treatment result
662
from cerebral insufficiency and occur within the
first 48 h (Lesage, 1986).
Management
The goal of CBS management is to recognize
at-risk patients, use diagnostic studies to
further determine risk, and treat in earlier
stages to prevent acute (type III) rupture
(Powitzky et al., 2010). The patient’s risk for
cerebral ischemia must be evaluated prior to
treating. Ischemia risk can be determined by a
balloon test. If the balloon test does not reveal
risk for ischemia, embolization is the treatment
option of choice. Endovascular therapy
provides the best option for prevention and
acute management of CBS in patients with head
and neck cancer (Powitzky et al., 2010).
Embolization with a balloon or coil is associated
with decreased mortality and 15–20%
neurologic morbidity (Chaloupka et al., 1996;
Lesley et al., 2004; Powitzky et al., 2010). Open
surgery with resection and reconstruction or
carotid artery ligation has a high risk of
hemodynamic instability and decreased
cerebral perfusion with neurologic morbidity
rates as high as 60% (Charbel et al., 1999;
Citardi et al., 1995). Surgical management may
also be challenging in the setting of previously
irradiated tissue due to fibrosis and risk for
poor wound healing (Chang et al., 2007). In the
case of an exposed artery, flap placement may
be necessary (Powitzky et al., 2010). If the
663
balloon test identifies high risk for ischemia
(decreased cerebral flow <20%) or if the patient
is unable to tolerate the balloon test, stent
placement is a more appropriate choice.
Performing a balloon occlusion test may not be
feasible in emergency cases or in cases of
hemodynamic instability. Use of stents requires
favorable anatomic conditions including patent
femoral and iliac artery anatomy to allow
placement of a large-bore sheath; nontortuous
aortic arch and branches; no carotid stenosis;
noncontaminated
wound;
and
no
contraindication to antiplatelet therapy (Chang
et al., 2007; Powitzky et al., 2010).
Self-expandable stents provide immediate
hemostasis with minimal neurologic morbidity.
Use of stents in the emergency setting may
allow for stabilization of the patient and
additional time to plan further, definitive
management (Chang et al., 2007). Immediate
complications include stroke, asymptomatic
thrombosis of the carotid artery; and long-term
complications include rebleeding, brain abscess
formation, and carotid thrombosis. Long-term
safety of stents has been questioned based on
rebleeding and thrombosis rates (Chang et al.,
2007). Based on this information, stents should
be reserved for emergency management.
Further study on appropriate antimicrobial
prophylaxis to minimize wound infection and
optimize use of antiplatelet therapy is needed to
improve long-term safety (Chang et al., 2007;
Kim et al., 2006).
664
In the case of acute CBS, the provider should
use a gloved finger to apply pressure to the site
of bleeding until definitive treatment can be
executed. The patient should be placed in
Trendelenberg
position
(Lesage,
1986).
Aggressive fluid resuscitation should be
employed to maintain blood pressure and blood
pressure should be monitored frequently.
Mortality rates during ligation procedures are
increased in the setting of hypotension and
hypotension is the greatest predictor of poor
outcomes (Powitzky et al., 2010). Any at-risk
patient should have a proactive plan for
managing CBS including prn orders for
sedation and pain management. Additionally,
supplies to manage CBS should be kept at or
near the patient’s bedside and include gloves,
gown, face shield, and goggles; large sterile
dressings;
suction
equipment;
cuffed
tracheotomy tube and 10 ml syringe; equipment
to place and maintain a large-bore IV; oxygen
equipment;
and
dark-colored
towels.
Emergency management may necessitate
placement of a cuffed tracheostomy to protect
the patient’s airway and provide internal
pressure on the source of bleeding. There is no
evidence that bedrest prevents or delays
rupture (Lesage, 1986). However, activities
such as heavy lifting and straining should be
avoided. Preventative management should
include strategies to minimize straining (e.g.,
Bowel regimens), coughing (antitussives), and
nausea/vomiting (antiemetics). The experience
665
of a CBS is often stressful and traumatic for
patients, family, and staff. Appropriate
supportive resources should be employed
including pastoral care and social work.
There are no prospective or comparison studies
examining the most appropriate management
of CBS. The available data are based on small
studies, many of them retrospective. Larger,
prospective studies are needed to help define
best practices.
Monitoring and treatment of oncology-related
critical care is complex. Interdisciplinary
planning and treatment require continual
surveillance of patient symptoms and attention
to subtle changes. This chapter has reviewed
the literature and recommended best practices
for a wide range of conditions affecting
oncology patients. Research continues and
changes in practice evolve daily.
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Chapter 12
End-of-life concerns
Kathy J. Booker
Millikin University, Decatur, IL., USA
Introduction
End-of-life (EOL) issues arise frequently in the
care of critically ill patients. However, those
who care for patients regularly in these units
may feel ill-prepared for early discussions or
management of differing opinions by patients
and family members, especially when transition
points develop regarding patient response to
treatment. Despite published guidelines on
EOL care (Truog et al., 2008), many clinicians
find communication surrounding limitations or
withdrawal of care difficult. Even oncology
practitioners have reported inadequate formal
preparation in how to deliver and discuss bad
health news (Baile et al., 2000).
Assessment and communication
issues
In a busy intensive care unit (ICU), assessments
are often predominately focused on the
physiological management of a patient’s
conditions. Understanding the totality of
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patient needs including psychosocial and
spiritual issues is extremely important in
critically ill adults. Guidelines on pain
assessment for those unable to communicate,
including adult patients who are intubated or
those with dementia, have been published
(Herr et al., 2006). Ongoing assessment of
behaviors or verbal indicators of pain is critical.
Anticipation of pain when implementing known
painful procedures in those with dementia or
intubated/unconscious patients is important.
Herr et al. (2006) noted that the poor
correlation of vital sign changes with degree of
pain makes assessment more difficult. For
patients who are intubated or unconscious,
behavioral indicators may include facial
grimacing, frowning, wincing, and physical
movement or tearing and diaphoresis.
Undertreatment of pain remains an issue in
care and must be vigilantly assessed in patients
both able and unable to express pain aloud.
Guidelines advanced by Herr et al. (2006)
include strategies for pain assessment
incorporating potential causes, observations of
behaviors, use of analgesic trials, and an
overview of published behavioral assessment
tools. For patients with dementia, examination
of causes and behaviors associated with pain
and the collaboration with families who know
the patient well are recommended strategies to
ensure pain is managed as an ethical imperative
for all patients (Herr et al., 2006).
691
Other symptoms, such as dyspnea, have also
been reported to be undertreated by health-care
providers. The American Thoracic Society
(ATS) published clinical guidelines for palliative
care in patients with respiratory diseases and
critical illnesses (Lanken et al., 2008). These
are helpful in outlining the parameters of
movement from curative–restorative forms of
care to palliative care and the core
competencies expected in pulmonary and
critical care clinicians. Mularski et al. (2010)
examined palliative care for dyspnea and
reviewed over 40 instruments used for rating
dyspnea, determining that none of these scales
was ideal for use in palliative care. This review,
commissioned by the Agency for Healthcare
Research and Quality (AHRQ) and supported
by the National Cancer Institute, was a project
for the development of a framework for
assessing EOL quality indicators in cancer care
(Mularski et al., 2010). These authors identified
the Numerical Rating Scale, a ranking
numerical scale from 0 to 10, similar to
pain-rating scales commonly employed in many
care areas, as it is easy for most patients to use
and applicable across a number of settings,
from critical care to hospice. Its major
limitation is the use of a one-dimensionality
assessment of dyspnea, which is often complex
and
involves
additional
symptoms
concurrently.
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Mularski et al. (2010) also identified the
Respiratory Distress Observation Scale (RDOS)
for potential use in cognitively impaired
patients. Campbell, Templin, and Walch (2010)
evaluated the RDOS in patients with respiratory
conditions referred for inpatient palliative care.
While a few of the patients had severe distress,
the RDOS was found to accurately reflect
changes in treatment reflective of respiratory
symptoms and had acceptable reliability
(Chronbach’s alpha = 0.64). Since this tool does
not require patient self-report and includes
quick analysis of multiple observable
symptoms, including heart rate, respiratory
rate, respiratory effort and patterns, and nasal
flaring, further testing in critically ill patients at
the EOL is promising (Campbell, Templin, and
Walch, 2010). It should not be used when
patients are receiving paralytic agents or when
self-report is possible.
Family presence
The American Association of Critical Care
Nurses (AACN, 2013) provides resources online
for evidence-based practice guidelines. Practice
alerts compile literature support for issues
important to quality care in critical care units.
These guide critical care practitioners to
examine policies and consider inclusion of
family members for visitation, involvement in
care,
and
allowing
presence
during
resuscitation and invasive procedures (AACN,
693
2013). Permissive family presence during
resuscitation is also endorsed in a review by
Doolin et al. (2010). See also Chapter 1.
Advanced directives
Since the passage of the US Uniform Patient
Self-Determination Act (PSDA) in 1990
(Omnibus Budget Reconciliation Act, 1990),
health-care organizations receiving funding
through Medicare and Medicaid are required to
inform patients upon admission about the right
to refuse treatment and institutional policies
regarding advanced directives. This action may
be handled by admission personnel and is easily
overlooked as patients are being admitted to
critical care units due to intensive focus on
patients’ clinical condition and the need for
rapid interventional care. In the midst of a
critical event, identifying and supporting a
patient’s right to refuse treatment is difficult
and often deferred in an effort to save a life.
Johnson et al. (2012) studied reasons for
noncompletion of advanced directives in 505
patients admitted to cardiac intensive care in
North Carolina. They found that over 64% of
the patients did not have an advanced directive
upon admission but 45.5% of these patients had
discussed their wishes with the person
designated to serve as the power of attorney by
North Carolina state guidelines. Patients with
advanced directives on admission were more
likely to be over 65, Caucasian, have higher
694
numbers of comorbid conditions, and less likely
to have a family member present upon
admission. Johnson et al. (2012) noted the
difficulty in having meaningful discussions of
EOL issues during a stressful time such as
admission to an ICU and recommended that
recognition of cultural issues affecting
individual decisions as well as supportive
conversations guided better implementation of
the PSDA requirement.
Surrogate decision making
In the absence of advanced directives and when
patients are unable to make their own
decisions, most states provide for surrogate
decision making. Truog et al. (2008) reviewed
the US court cases that have influenced this
area of practice and observe that “when patients
cannot make decisions for themselves,
decisions are made on their behalf by
surrogates, using either the ‘substituted
judgment standard’ (if the patient’s values and
preferences are known) or the ‘best interests
standard’ (if they are not). While these
decisions are often reached by consensus with
the patient and family, patients do have an
opportunity to designate a specific individual as
a healthcare proxy” (p. 954). Sadly, many adults
do not plan ahead for such situations and the
decision for care and treatment must occur at
the
bedside
under
less-than-ideal
circumstances. Adequate time and resources
695
must be made available to surrogates. Many
hospitals have dedicated pastoral support,
strong interdisciplinary care teams, and may
also have ethics committees with representation
across disciplines and from the lay community
to assist in difficult decisions regarding critical
care.
AACN offers a number of online resources to
support clinicians in helping with patient and
family EOL discussions (AACN, 2011). One
resource offers discussion points on advance
directives and talking points to assist patients
and families in discussing and enacting
documents (Westphal and Wavra, 2005).
Another important reference is the published
guidelines for quality palliative care (National
Consensus Project for Quality Palliative Care,
2013).
As an essential element in effective treatment of
patients and families in the critical care unit,
communication skills are extremely important
for critical care personnel. When EOL issues
arise, prior communication patterns are often
accentuated so that families who have
unresolved issues prior to a loved one’s critical
illness will struggle with the decisions that must
be made when decisional capacity is lost. Truog
et al. (2008) discussed the ethical principles
and strategies that may help clinicians improve
communication in the ICU (see Table 12.1).
Based on the primary ethical principles
696
surrounding withholding versus withdrawing
treatment, killing versus allowing to die, and
intended versus unforeseen consequences of
treatment, Truog et al. (2008) reviewed these
issues from the perspective of life-sustaining
treatments and decisions that must often be
handled at the EOL in critical care units.
Table 12.1 Strategies for improving end-of-life
communication in the intensive care units.
Strategies for improving end-of-life
communication in the intensive care unit (ICU).
From Truog et al. (2008). © LWW.
Communication skills training for
clinicians.
ICU family conference early in ICU course
(Lilly et al., 2000)
Evidence-based recommendations for
conducting family conference:
Find a private location (Pochard et al.,
2001).
Increase proportion of time spent
listening to family (McDonagh et al.,
2004).
Use “VALUE” mnemonic during family
conferences (Lautrette et al., 2007).
Value statements made by family
members.
Acknowledge emotions.
697
Listen to family members.
Understand who the patient is as a
person.
Elicit questions from family
members.
Identify commonly missed opportunities
(Curtis et al., 2005; West et al., 2005).
Listen and respond to family
members.
Acknowledge and address family
emotions.
Explore and focus on patient values
and treatment preferences.
Affirm nonabandonment of patient
and family.
Assure family that the patient will not
suffer (Stapleton et al., 2006).
Provide explicit support for decisions
made by the family (Stapleton et al.,
2006).
Additional expert opinion
recommendations for conducting family
conference:
Advance planning for the discussion
among the clinical team.
698
Identify family and clinician
participants who should be involved.
Focus on the goals and values of the
patient.
Use an open, flexible process.
Anticipate possible issues and
outcomes of the discussion.
Give family support and time.
Interdisciplinary team rounds.
Availability of palliative care and/or ethics
consultation (Campbell and Guzman,
2003; Schneiderman et al., 2003).
Development of a supportive ICU culture
for ethical practice and communication
(Hamric and Blackhall, 2007).
The
use
of
strategies
to
improve
communication and adherence to ethical
standards
assist
all
members
of
multidisciplinary
teams
to
provide
compassionate, sensitive care to those who
need it in the critical care setting.
Delivering bad news
Giovanni (2012) reviewed policy issues
affecting EOL care in the United States and
identified the incongruence between many
patients’ wishes and the care often delivered in
699
critical care units. Giovanni identified current
US priorities for cost containment and the
growth of hospice movements contrasted with
wide geographical differences and disparity in
acute care services. The participation of nurses
in assisting families and the health-care team
during
difficult
conversations
and
decision-making is crucial.
Baile et al. (2000) developed and tested a
six-step model (SPIKES) for delivering bad
news to cancer patients, noting the low degree
of education and training among physicians for
successful models to deliver bad news in a
humane and caring way. The SPIKES model
includes the following steps:
Step 1: S—SETTING UP the interview—arrange
for some privacy; involve significant others; sit
down; make connection with the patient;
manage time constraints and interruptions.
Step 2: P—Assessing the patient’s
PERCEPTION—before discussing the medical
findings, the clinician uses open-ended
questions to create a reasonably accurate
picture of how the patient perceives the medical
situation.
Step 3: I—Obtaining the Patient’s
INVITATION—while a majority of patients
express a desire for full information about their
diagnosis, prognosis, and details of their illness,
some patients do not.
700
Step 4: K—Giving KNOWLEDGE and
information to the patient—warning the patient
that bad news is coming may lessen the shock
that can follow the disclosure of the bad news.
Step 5: E—Addressing the patient’s EMOTIONS
with empathic responses—when patients get
bad news, their emotional reaction is often an
expression of shock, isolation, and grief (Baile
et al., 2000, pp. 305–306).
This model may be applied to critical care
situations and when working with families of
critically ill adults who may have lost decisional
capacity. It may be taught as a strategy for
practitioners to systematically consider the
impact of bad news so that a humane and
caring approach is used in difficult situations.
Other resources for communicating with
families are available via the web site of the
Center to Advance Palliative Care (Weissman
and Meier, 2011). One strong reference on the
CAPC web site offers a program for
communication of difficult information in the
ICU. It incorporates the SPIKE framework as
one element in discussing bad news in critically
ill patients. The CAPC web site also offers many
references including selected hospital protocols,
pocket cards, and methods for establishing
family conferences.
Weissman and Meier (2011) published a
consensus report from the CAPC, which
identifies the need for more systematic
701
assessments to advance palliative care for those
facing life-limiting episodes during acute
hospitalizations. This document advances the
development of palliative assessment triggers
for admission and during each hospital stay for
patients who present with a potentially
life-limiting or life-threatening condition.
Within
this
consensus
document,
recommendations include targeted indicators
such as recurrent admissions, complex care,
functional declines, failure to thrive, home
oxygen therapy, out-of-hospital cardiac arrest,
and limited social support. The use of such tools
to address pending needs is strongly
encouraged
for
daily
rounding
and
interdisciplinary support.
Palliative care in the ICU
Palliative care is a philosophy of care that does
not equate to “comfort” measures or any
particular intervention of care. The ATS
published a clinical policy statement on
palliative care for patients with respiratory and
critical illness aimed to relieve suffering and
provide support to patients and families to
enhance quality of life (Lanken et al., 2008).
Palliative care is not limited to terminal care
and is not incompatible with critical care
delivery.
A national project endorsed by a number of
specialty medical and nursing organizations,
702
the National Consensus Project for Quality
Palliative Care (2013) has published the second
edition of clinical guidelines. These guidelines
offer a review of models of care that have been
successfully implemented across the nation and
clearly define variables and guidance for
clinicians interested in expanding their acumen
in this area. The guidelines outline the basic
assumptions, eight domains of quality care, and
a series of guidelines for each domain with a
focus on strong interdisciplinary support for
patients and families targeting professional
behavior and delivery of excellence in each area.
Domains and examples of each standard are
incorporated into Table 12.2 (National
Consensus Project for Quality Palliative Care,
2013). Within this document, each domain is
supported with a strong recommended reading
bibliography as well as exemplars from
programs that have attained best practices in
the recommended guidelines. This resource is
important to programs seeking excellence in the
development of comprehensive palliative care
programming.
Table 12.2 Domains of quality palliative care
and overview of clinical practice guidelines.
Adapted from NCPQPC (2009).
703
Domains of
quality
palliative
care
Examples of
clinical
practice
guidelines
Multidisciplinary
impact
1 Structure
and
processes of
care
Nine guidelines
are
recommended,
including plan
of care
suggestions,
assessment of
patient and
family,
needs-based
physical
environment
Goals, plan of care,
and assessment all
based on
interdisciplinarity
2 Physical
aspects of
care
One guideline
focused on
symptom
management
and outcomes.
Extensive
bibliography of
pain and
associated
symptom
management
and treatment
references
Clear incorporation
of patient, family,
and
interdisciplinary
team to skillfully
treat and evaluate
symptoms
3
Two guidelines Referrals to
Psychological focused on
health-care
704
Domains of
quality
palliative
care
Examples of
clinical
practice
guidelines
Multidisciplinary
impact
and
psychiatric
aspects of
care
education and
skillful
management of
psychiatric
comorbidities,
including
stress ,
anticipatory
grieving, and
coexisting
psychiatric
issues
professionals with
mental health
expertise,
incorporation of
family and
interdisciplinary
involvement,
including grief and
bereavement
services
4 Social
aspects of
care
One guideline
advising
comprehensive
social
assessment to
incorporate
family and
social service
support
Includes routine
family meetings,
comprehensive
social and cultural
assessments, and
interdisciplinary
cohesion
5 Spiritual,
religious,
and
existential
aspects of
care
One guideline
advising
regular, guided
assessment of
patient and
family
Advises referrals to
professions in
spiritual and
existential issues,
including those
with specialized
705
Domains of
quality
palliative
care
Examples of
clinical
practice
guidelines
Multidisciplinary
impact
concerns in
knowledge of rituals
this area,
or spiritual
including “life traditions
review,
assessment of
hopes and
fears, meaning,
purpose,
beliefs about
afterlife, guilt,
forgiveness,
and life
completion
tasks” (p. 58)
6 Cultural
aspects of
care
One guideline
focused on
cultural
understanding
and
incorporation
of patient/
family’s
cultural needs,
particularly
with respect to
“cultural
preferences
706
Strong emphasis on
communication;
incorporation of
interpreters, family
members, and
recommendation
that hiring practices
reflect community
cultural diversity
Domains of
quality
palliative
care
Examples of
clinical
practice
guidelines
Multidisciplinary
impact
regarding
disclosure,
truth telling,
and decision
making” (p. 65)
7 Care of the Three
imminently guidelines
dying patient covering
impending
death:
recognition,
communication
of end-of-life
concerns
honestly and
respectfully;
postdeath care
is respectful
and culturally
appropriate;
bereavement
plan is
activated
Interdisciplinary
involvement is
paramount; hospice
referrals, education,
referrals for funeral
arrangements, and
family support are
all interdisciplinary
8 Ethical and Three
legal aspects guidelines
of care
covering
general
Inclusion of
professional advise
on legal and
regulatory issues,
707
Domains of
quality
palliative
care
Examples of
clinical
practice
guidelines
Multidisciplinary
impact
guidance for
legal issues
regarding
surrogates,
decisional
capacity issues,
and ethical
issues
surrounding
debilitating
illness and
palliative care
guardianship, and
other legal
concerns; palliative
care team seeks to
prevent ethical
dilemmas whenever
possible through
interdisciplinary
involvement and
patient/family
support efforts
Palliative care is a philosophy of care and
treatment rather than a process linked to
clinical staging. Because of the long tradition of
interventional care in the critical care unit, care
providers may struggle with limitations to
aggressive management of care that may be
associated with palliative measures. However,
deliberate consideration of caregivers’ personal
perspectives and a thorough understanding of
published guidelines should be required as part
of orientation programs prior to working in an
ICU practice. The ATS clinical policy (Lanken et
al., 2008) distinctly addresses how to ethically
and compassionately shift from a care modality
of aggressive curative/restorative care to a
708
palliative care perspective. Table 12.3 highlights
core competencies for clinicians recommended
within this document.
Table 12.3 Core competencies in palliative
care for pulmonary and critical care clinicians
recommended by the Ad Hoc ATS End-of-Life
Care Task Force.
Reprinted with permission of the American
Thoracic Society from Lanken et al. (2008, p. 914,
table 2). © American Thoracic Society.
Communication and relationship
competencies
Ability to communicate with empathy and
compassion
Ability to guide the family during the
patient’s final hours
Ability to help the family during their period
of grief and bereavement
Ability to identify the patient’s values, life
goals, and preferences regarding dying
Ability to identify psychosocial and spiritual
needs of patients and families and resources
to meet those needs
Advance care planning with patient and
family
Coordination of care and ability to work
effectively in an interdisciplinary team
709
Cross-cultural sensitivity and cultural
competence
Information sharing, including ability to
break bad news skillfully
Clinical and decision-making competencies
Ability to apply sound ethical and legal
decision making to situations arising from
symptom management and withholding and
withdrawing life-sustaining therapy
Ability to resolve conflicts over futility,
requests for physician-assisted suicide, or
active euthanasia
Establishing an overall medical plan
including palliative care elements
Ability to prognosticate survival and
expected quality of life
Managing withholding and withdrawing
life-sustaining therapy and the patient’s
impending death
Pain and nonpain symptom management,
including dyspnea
Using the shared decision-making model
with families and other surrogates for
patients lacking full decision-making
capacity (President’s Council)
710
Symptom management
Patients in the ICU often experience rapid
deterioration due to the complexity of critical
conditions, many of which may lead to
multiorgan system failure. Early identification
of patient and family position and thoughts
regarding aggressive resuscitation efforts is
important from the time of admission. When
decisions are made to limit aggressive care,
symptom control is often essential, including
management of pain, dyspnea, temperature
changes, heart rate, and blood pressure
extremes. In many cases, anxiolytics and
opioids are helpful in controlling symptoms.
Clinical guidelines generally support the use of
small intravenous doses with titration for
control of symptoms.
Within the recommendations advanced by
Truog et al. (2008), guidelines for opioids and
sedatives are advanced to manage pain,
dyspnea, and agitation. In addition, use of
nonpharmacologic interventions is enlisted,
including sleep promotion, reductions in noise
and lighting, and encouraging family presence
during periods of agitation or delirium.
The AACN has also been active in promoting
nursing skills in palliative care including an
e-learning course available online for a nominal
fee for individuals to learn more about
palliative and EOL care (AACN, 2011). This
course uses interactive patient scenarios to
711
bring to life modules on symptom management,
communication, conflict resolution, and
withdrawing and withholding life support.
The End-of-Life Nursing Education Consortium
(ELNEC) (AACN, 2011) has facilitated the
education of thousands of nurse educators,
nursing students, and practicing nurses,
focusing on improving communication among
health professionals and highlighting nursing’s
key role in working to facilitate EOL decisions
(Wittenberg-Lyles, Goldsmith, and Ragan,
2011). Over 12 000 nurses and other
health-care professionals have used the ELNEC
materials, which consist of eight modules on
nursing care at the EOL (AACN, 2011).
Brain death
Despite the aggressive life-saving efforts within
the critical care unit, patients may progress to
brain death. With the ability to maintain
respiration on mechanical ventilators, the
development of brain death is difficult for
family members to understand and the critical
care team is challenged to provide clear
direction and support in these situations.
Wijdicks et al. (2010) published guidelines on
determining brain death in adults. In these
guidelines, the lack of an evidence base for
determining brain death is acknowledged, and
important review of studies that have employed
alternative diagnostic methods such as
712
magnetic resonance imaging and computed
tomography evidence of brain death and
multiple differential diagnoses are presented to
ensure that patients truly have irreversible
causes of coma. With the lack of evidence for
accepted medical standards, the authors
propose a clinically based set of guidelines for
determination of brain death, including
methods for clinical evaluation and steps to
ensure
that
appropriate
methods
are
implemented.
Documentation
and
determination of timing of brain death are also
offered (see Table 12.4). These guidelines may
promote a more consistent method of brain
death determination.
Table 12.4 Checklist for declaring brain death,
consistent with these guidelines.
Reprinted with permission from Wijdicks et al.
(2010). © LWW.
Checklist for determination of brain
death
Prerequisites (all must be checked)
Coma, irreversible and cause unknown
Neuroimaging explains coma
CNS depressant drug effect absent (if
indicated on toxicology screen; if barbituates
given, serum level <10 µg/ml)
No evidence of residual paralytics (electrical
stimulation if paralytics used)
713
Checklist for determination of brain
death
Absence of severe acid–base, electrolyte,
endocrine abnormality
Normothermia or mild hypothermia (core
temperature >36 °C)
Systolic blood pressure ≥100 mmHg
No spontaneous respirations
Examination (all must be checked)
Pupils nonreactive to bright light
Corneal reflex absent
Oculocephalic reflex absent (tested only if
cervical spine integrity ensured)
Oculovestibular reflex absent
No facial movement to noxious stimuli at
supraorbital nerve, temporomandibular joint
Gag reflex absent
Cough reflex absent to tracheal suctioning
Absence of motor response to noxious stimuli
in all four limbs (spinally mediated reflexes
are permissible)
Apnea testing (all must be checked)
Patient is hemodynamically stable
714
Checklist for determination of brain
death
Ventilaor adjusted to provide normocarbia
(PaCO2, 34–45 mmHg)
Patient preoxygenated with 100% FiO2 for >10
min to PaO2 > 200 mmHg
Patient well oxygenated with a PEEP of 5 cm
H 2O
Provide oxygen via a suction catheter to the
level of the carina at 6 l/min or attach T-piece
with CPAP at 10 mm H2O
Disconnect ventilator
Spontaneous respirations absent
Arterial blood gas drawn at 8–10 min, patient
reconnected to ventilator
PCO2 ≥ 60 mmHg, or 20 mmHg rise from
normal baseline value
OR:
Apnea test aborted
Ancillary testing (only one needs to be
performed) to be ordered only if clinical
examination cannot be fully performed
due to patient factors, or if apnea
testing is inconclusive or aborted)
Cerebral angiogram
HMPAO SPECT
715
Checklist for determination of brain
death
EEG
TCD
Time of death (DD/MM/YY)
___________________________
Name of physician and signature
_______________________
In the United States, broadly changing
health-care delivery is anticipated over the
coming decade. With rising health-care costs
and increased percentage of the gross domestic
product spent on health care, EOL care is under
considerable scrutiny. Wunsch et al. (2009)
compared the use of ICU services during
terminal hospitalizations between England and
the United States. While a greater percentage of
deaths occurred during hospitalization in
England, only 10% were experienced in ICUs
compared with 47% in the United States, with
the largest differences among elderly persons.
Wunsch et al. (2009) identified the many
factors that influence differing patterns,
including legal decision making for those
unable to make health-care decisions, cultural
norms, and physician philosophies affecting
aggressiveness of treatment. Clearly, shifts in
ICU utilization can be anticipated in the near
future in the United States, and these will be
difficult decisions to make without considerable
716
efforts to improve collaboration of all
health-care providers, patients, and families to
meet the palliative care needs and promote safe
and high-quality care at the EOL.
In summary, EOL issues abound in the critical
care unit and many resources exist to prepare
clinicians to develop skills for promoting
compassionate patient and family decision
making. Working with difficult decisional issues
is a continual challenge in the critical care
environment but it also brings rewards when
patients and families express satisfaction with
respectful, competent care. While many models
and guidelines have been developed, the
commitment of the critical care team is central
to improving EOL care. Further research is
needed to evaluate interventional and
communication
patterns
that
support
high-quality, ethically supportive, and effective
EOL care.
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722
Chapter 13
Monitoring for overdoses
Linda M. Dalessio
Western
Connecticut
Danbury, CT., USA
State
University,
Introduction
General management of drug overdoses
The general management for all drug overdoses
is to support airway, breathing, and circulation.
Intubation and ventilation may be required.
Circulatory support is generally accomplished
with intravenous (IV) crystalloid fluids. If
hypotension
is
unresponsive
to
fluid
resuscitation, use of vasopressor agents may be
needed. Finger stick glucose testing should be
done in all patients with altered mental status.
If opioid or benzodiazepine overdose is
suspected, the use of naloxone or flumazenil
(Romazicon) may be needed. In the case of
tricyclic
antidepressant
(TCA)
or
antiarrhythmic overdose use of sodium
bicarbonate,
hypertonic
saline,
and/or
hyperventilation may be warranted. All
treatment centers for overdose management
should check with Poison Control Centers
designated by the state. This chapter is not
723
intended to guide all treatment and
management of overdoses or toxic exposure.
However, monitoring critically ill patients for
overdose symptoms and understanding the
management of overdoses are helpful to critical
care practitioners.
A detailed history should be obtained from the
patient (if able), family or significant other, law
enforcement, and Emergency Medical Service
(EMS) personnel. If pertinent, efforts should be
made to obtain prescription bottles, or empty
bottles of substances to quantify amounts of
drugs taken. It may be necessary to obtain
pharmacy information to have a complete list of
drugs prescribed and amounts filled. Most drug
overdoses affect the cardiovascular and central
nervous system (CNS). If at all possible,
toxidromes should be identified as these can
help identify the drug toxin, especially in
circumstances in which the toxin is unknown.
These will be explored within this chapter.
Drug screening
In most hospitals, drug screens usually only
involve five primary substances: opioids,
marijuana, amphetamines, barbiturates, and
cocaine. There are thousands of toxic
substances in the world. Certain drug tests are
available for some toxic substances but may
only be available at state-level toxicology
centers. Poison Control Centers guide
practitioners
in
identifying
substances,
724
monitoring parameters, and safety issues in
treatment and follow-up. The most common
toxic substance overdoses seen in critical care
settings
include
acetaminophen,
benzodiazepines,
opioids,
alcohol,
antidepressants, certain street drugs, and
stimulants. Separate testing is ordered for
salicylate and acetaminophen levels. Hospital
laboratories may need to test separately for
methadone.
Activated charcoal, gastric lavage, and
cathartics (whole bowel irrigation) may be
beneficial in some instances of drug ingestion.
Gastric lavage has fallen out of favor by most
toxicologists due to its lack of benefit and risk of
aspiration. Activated charcoal may be
considered if drug ingestion has occurred
within 1 h. Studies have shown that when
charcoal is given within 30–60 min following
ingestion, 50% of a drug may be recovered.
Once the drugs have passed through the pylorus
into the small intestine, amounts recovered are
much smaller (Gussow, 2009). Others have
warned of a higher risk of charcoal aspiration,
which can lead to chemical pneumonitis.
Charcoal works by binding drugs to its large
surface area. The general rule is to give a 10:1
ratio of activated charcoal or 1–2 g/kg of body
weight. Charcoal does not effectively bind
organic salts such as iron or lithium. Gastric
lavage should be employed if the benefit
725
outweighs the risk. It should be done within the
first couple of hours post ingestion using a
large-bore nasal gastric tube. Risks include
aspiration, esophageal perforation, hypoxia,
laryngospasm, misplacement of tube into
respiratory tract, and discomfort. Cathartics
should
be
used
following
charcoal
administration
to
prevent
constipation.
Whole-bowel irrigation using Golytely (2 l/h)
can be used in instances of ingestion of
sustained-release
medications,
iron,
or
enteric-coated
substances
(Givens
and
O’Connell, 2007). Collaboration with state
Poison Control Centers should be considered
for all instances of poisoning/ingestion of
known and unknown substances. Dialysis or
use of molecular adsorbent recirculating system
(MARS) has been effective in overdoses of
barbiturates, lithium, metformin, salicylates,
theophylline, toxic alcohols, isopropanol,
valproic acid, carbamazepine, diltiazem,
phenytoin, and mushroom poisoning (DePont,
2007).
Additional issues may involve law enforcement
in cases of intentional poisoning by others and
notification of state agencies may be needed for
the protection of children or patients with
psychiatric disabilities. Social services within
the hospital setting should be consulted.
Mandatory referral is needed to psychiatry in
all instances of overdose so it may be
determined whether the overdose was
726
accidental or deliberate and interventions may
be started.
It is impossible to cover every possible overdose
within this chapter and newer therapies are
under investigation. Drug overdoses or toxin
exposure may be accidental or intentional.
Primary organic substance overdoses are
reviewed. All emergency and critical care
personnel should become familiar with local
and regional Poison Control Center contacts.
New and emerging therapies
New and exciting research into the use of
intravenous lipid emulsion (ILE) therapy for
certain drug overdoses is under way. The
mechanism of action of ILE is thought to be a
reduction in free drug levels and toxicity. ILE
works by expanding the liquid phase
availability, which acts as a large vascular liquid
component and soaks up the lipid-soluble toxin
like a sponge. Another action is inhibition of
drug transport across membranes and
facilitation of fatty acids into the mitochondria.
This results in maintenance of cellular energy
and increased inotropic support for the
poisoned myocardium. Antidotal use of ILE is
investigative and is not approved by the Food
and Drug Administration (FDA), but it has
recently become part of several professional
guidelines for the treatment and management
of local anesthetic systemic toxicity (LAST).
Drug overdoses in which this therapy may be
727
used are TCAs, some atypical psychiatric drugs,
calcium channel blockers (CCBs), beta blockers,
aminodarone,
barbiturates,
and
certain
anesthetic drugs. There have been several case
reports in which this therapy has been used
when standard supportive protocols, advanced
cardiac life support (ACLS) protocols, and
conventional toxicology for overdose have not
been effective in the initial resuscitative efforts
with patients who have taken an overdose of a
lipophilic cardiotoxin (Cave, 2011).
The most convincing body of evidence for
treating LAST is in overdoses of bupivacaine
and lidocaine. Complications from this disorder
can include cardiovascular and CNS collapse,
which has been generally treated with a
prolonged
course
of
cardiopulmonary
resuscitation efforts that are often unsuccessful.
Major
anesthesia
organizations
have
incorporated the use of ILE in the treatment of
LAST. Current guidelines for administration are
1.5 ml/kg bolus followed by an infusion of 0.25
ml/kg/min of ideal body weight of a 20% lipid
emulsion. If hemodynamic instability is still
present, boluses can be repeated up to three
times, 3–5 min apart (Ozcan and Weinberg,
2011). Avoidance of vasopressin and use of
low-dose epinephrine may also be effective in
the setting of LAST (Rothschild et al., 2010).
Lipid emulsions with long chain fatty acids have
been shown to have an advantage over medium
728
chain fatty acids. Adverse effects of ILE are rare
and reporting has included elevated liver
function tests (LFTs), amylase, and symptoms
associated with acute respiratory distress
syndrome, allergic reactions, and gross
hematuria. At initial infusion, intralipid can
increase body temperature and cause chills,
nausea, and vomiting. If this occurs, therapy
should
be
discontinued.
Relative
contraindications to therapy include egg
allergy,
impaired
lipid
metabolism,
uncompensated diabetic mellitus, pancreatitis,
liver insufficiency, hypothyroidism if in relation
to hypertriglyceridemia. Case reports of fat
emboli have also been reported (Muzawazi and
Manickam,
2012).
Lipid
emulsion
administration can also interfere with certain
laboratory tests and cause falsely elevated levels
of total hemoglobin and methemoglobin (Ozcan
and Weinberg, 2011). If ILE is administered
during cardiac arrest (dosages have ranged in
case reports from 50 ml of 20% lipid emulsion
to 200 ml), clinicians must be aware that it will
also bind lipid-soluble cardiac resuscitative
drugs such as amiodorone and lidocaine (Ozcan
and Weinberg, 2011).
High-dose insulin/glucose euglycemia (HIE)
therapy is also being used in calcium channel
and beta blocker overdose. This therapy has not
been approved but has worked in animal and
case studies and appears safe. The mechanism
of action is thought to be increased inotropic
729
effects within the cardiovascular system that
involves calcium and the P13K pathway. HIE
therapy causes increased inotropic effects,
increased intracellular glucose transport, and
vascular dilatation. The vasodilatation effect of
insulin is thought to be due to the enhancement
of endothelial nitric oxide synthase activity and
its effects on P13K, which is a major
insulin-signaling
pathway.
Insulin
also
enhances microvascular perfusion at the
capillary bed and decreases vascular resistance,
which results in improved cardiac output
(Engebretsen et al., 2011).
Doses suggested in case studies are 1 μ/kg
insulin bolus followed by 1–10 μ/kg/h. This is
run concurrently with dextrose infusion, which
may be needed for up to 24 h after insulin
therapy is completed (Page, Hacket, and
Isbister, 2009). Major adverse side effects are
hypoglycemia and hypokalemia. Frequent
monitoring of blood glucose levels and
potassium levels is needed with this therapy.
This therapy is recommended initially in beta
blocker and CCB poisoning but pitfalls exist
(Smollin, 2010).
Another newer therapy that is being used is
octreotide
for
sulfonylurea
overdose.
Sulfonylureas are one of the most commonly
prescribed antidiabetic agents. Estimated
overdose numbers approximate 4000 patients
annually who are reported to Poison Control
730
Centers (Spiller and Sawyer, 2006). Overdose
of sulfonylurea affects B cells in the pancreatic
islets causing hypoglycemia and inhibition of
potassium channels, which causes opening of
voltage-gated calcium channel and an influx of
calcium ions. This triggers a cascade of events
that produces exocytosis and increased insulin
secretion, resulting in a hyperinsulinemic state
and hypoglycemia. Peak plasma levels usually
occur within 1–8 h and hypoglycemia usually
occurs within 8 h. In the case of renal failure,
symptoms can be delayed by several days. Signs
and
symptoms
include
hypoglycemia,
tachycardia, diaphoresis, and CNS symptoms.
Activated charcoal can be given if ingestion is
within 1–2 h. Treatment should be started
early, and patients should be allowed to eat and
drink. IV dextrose should only be given for
blood sugars less than 60 mg/dl with
symptoms. For hypoglycemia that is refractory
to dextrose administration, octreotide should
be administered. Actions of octreotide help
bind somatostatin subtype G receptors in the
pancreatic B cells, which inhibits the opening of
the calcium channels and decreases calcium
flux, which reduces the release of insulin from B
cells (Roberts, 2010). Optimal dosages have not
been established but effective treatment with
50–100 μg subcutaneously every 8 h for 24–48
h have been given with success (Lheureux et al.,
2005).
731
Indexing of drug and toxins seen
in overdoses
Common drug ingestions will be covered using
the following summary categories
Drug overview
Symptoms of overdose
Diagnostic testing and monitoring
Antidotes/evidence-based treatment/use of
binding agents
Clinical pearls for patient management and
treatment
Acetaminophen
Drug overview
Acetominophen is an over-the-counter (OTC)
analgesic that also comes in extended-release
forms and is often combined with opiates or
other cold and fever medications. It is rapidly
absorbed with peak levels in 30–120 min.
Therapeutic dose is no more than 4 g/24 h.
Absorption may be delayed in extended-release
forms. Elimination half-life is 1–3 h after
ingestion and up to 12 h in acute overdose. A
Tylenol nomogram should be used for
prediction of hepatotoxicity after acute
overdose, within a 24 h window of ingestion;
this is widely available on the Internet.
732
Symptoms of overdose
Acute overdose may be seen with ingestion of
more than 140 mg/kg or 7.5 g in a 24 h period
or as a single amount. Symptoms may be
nonspecific or absent early and then progress to
include nausea, vomiting, malaise, and
anorexia. On day 3, elevated transaminases,
jaundice, right upper quadrant pain, and
elevations in bilirubin can occur. With massive
overdose, altered mental status and metabolic
acidosis can occur. If liver injury progresses to
fulminant hepatic failure, symptoms of
encephalopathy,
lactic
acidosis,
and
coagulopathy will develop. The patient will
either enter the recovery phase or progress to
hepatic failure and will need to be evaluated for
a liver transplant. Referral should be made
early in diagnosis to the gastrointestinal (GI) or
hepatologic service.
Diagnostic testing and monitoring
Acetaminophen levels should be obtained every
6–8 h, and complete metabolic panel, baseline
acetylsalicylic acid (ASA) and drug toxicology
screening should be completed. LFTs and
coagulopathy should be completed daily until
acetaminophen levels are undetectable and risk
of toxicity is over. Testing should be based on
individual presentation.
733
Antidotes/binding agents
Mucomyst (N-acetylcysteine IV infusion or
orally) is the antidote of choice and is ideally
administered within 8–10 h of ingestion and
can be given up to 16 h post ingestion (Chun et
al., 2009). Patients should also receive
lactulose, Golytely, or any laxative/cathartic to
induce
diarrhea
for
overdoses
with
extended-release forms of acetaminophen.
Activated charcoal can be given within 4 h of
ingestion or there are co-ingestions of other
drugs. Charcoal can absorb up to 50% of
acetaminophen. Charcoal dose is 1 g/kg for a
total of a 50 g dose. Mucomyst oral loading
dose is usually 140 mg/kg of the 10–20%
solution. Maintenance oral dose is usually 70
mg/kg every 4 h for 17 doses, which is usually
for 72 h. IV dosing may be the preferred
method. The loading dose is 150 mg/kg over 15
min followed by 50 mg/kg over 4 h, then 100
mg/kg over 16 h. New therapies for infusion are
commonly given over 21 h, with the loading
dose given over 60 min to decrease the risk of
anaphylactic reactions (Hodgman and Garrard,
2012). If acetaminophen levels continue to rise,
dosing may be continued past 16 h.
Mucomyst acts as a sulfhydryl group donor and
substitutes the liver’s usual sulfhydryl donor,
glutathione. Mucomyst is able to bind and
detoxify the intermediates of metabolism and
may reduce the toxic intermediates. Mucomyst
734
is most effective when given early in the setting
of overdose. Some of the side effects are nausea
and vomiting, especially with oral preparations.
Clinical Pearls
Approximately 10–20% of patients can
develop an analphylactoid reaction to
Mucomyst that consists of hives and
urticaria. The infusion is usually stopped; the
patient is given Benadryl 1 mg/kg up to 50
mg, then the infusion is restarted. If patients
develop hypotension or respiratory distress
from IV Mucomyst, oral dosing is usually
tolerated better. If a patient vomits within 1 h
of a dose, the dose should be repeated.
Treatment can be stopped when
acetaminophen levels are undetectable,
international normalized ratio (INR) is less
than 2, and the Alanine Aminotransferase
(ALT) has returned to normal or has
decreased more than 50% of peak value.
Elevation of INR by itself can be misleading
as elevated acetaminophen levels and
therapeutic levels of Mucomyst can cause
elevation of INR. There are newer treatments
for fulminent liver failure from
acetaminophen and other causes that are
available to select patients at several
hospitals across the United States called
735
MARS. This system uses an extracorporeal
technique with albumin exchange for the
removal of toxins that is similar to
hemodialysis. Consultation with hepatology
and referral to these trial facilities may be
life-saving when liver for transplant is not
immediately available (DePont, 2007).
Clinical use of Mucomyst in patients who
present beyond the 10 h period of ingestion
or in patients who are already showing signs
and symptoms of liver injury is becoming
more controversial due to a concern that late
presenters may have changed kinetics to
Mucomyst, which may reduce its efficacy and
lead to adverse hemodynamic changes. This
is postulated to cause impairment of
regeneration in the liver (Athuraliya and
Jones, 2009; Yang et al., 2009).
Salicylates and nonsteroidal
anti-inflammatory drugs
Drug overview
Salicylates are a class of drug that includes a
variety of medications used for their analgesic
and anti-inflammatory properties. Aspirin
(ASA) overdose commonly causes an increased
anion gap acidosis. Toxic effects of nonsteroidal
anti-inflammatory drugs (NSAIDs) usually
occur within 1 h and patients who have diseases
736
with low protein levels are at increased risk of
toxicity due to protein binding and drug
distribution. Usually symptoms of NSAID
poisoning are mild and nonspecific. Toxic levels
usually produce mental status changes. The
half-life is 1–50 h depending on the NSAID
ingested. ASA (aspirin) is hydrolyzed to salicylic
acid, which stimulates the respiratory center
and produces hyperventilation. Salicylates also
cause uncoupling of oxidative phosphorylation
at the cellular level. Salicylates are metabolized
in the liver to inactive metabolites. The
remaining amounts are excreted unchanged in
the urine.
Nonsalicylate NSAIDs are rapidly absorbed
after ingestion and metabolites are not
saturable; they are highly protein-bound, and
elimination follows first-order kinetics. Massive
ingestion is usually 6 g in an adult.
Symptoms of overdose
Symptoms with salicylate overdose can begin
within 1–2 h after ingestion but can be delayed
in
sustained-release
formulas.
Nausea,
vomiting, tinnitus, hearing loss, coma, seizures,
respiratory alkalosis followed by metabolic
acidosis, increased levels of lactic acid,
tachycardia, tachypnea, fever, hypotension, and
acute renal insufficiency can occur. Symptoms
may also include nausea, vomiting, tinnitus,
tachycardia, diaphoresis, and abdominal
discomfort.
737
Cases of moderate poisoning result in
acid–base balance being either normal or
alkaline. Electrolyte disturbances may show
combined respiratory alkalosis and metabolic
acidosis with increased anion gap. Common
symptoms include an increase in GI and
neurological symptoms. Signs and symptoms of
severe poisoning include seizures, coma, shock,
respiratory depression, and noncardiogenic
pulmonary edema. Severe renal dysfunction
may develop.
Monitoring
Serum salicylate levels should be obtained every
2 h for the first 4–8 h, then every 6–8 h once
levels are declining. Serum concentrations over
20 mg/dl saturate the liver and elimination
changes from first-order to zero-order kinetics.
This causes the half-life to increase from 2.5 h
to an upper limit of 40 h. Renal elimination is
then conducted. Levels of more than 30 mg/dl
are associated with mild toxicity. Severe levels
are 75 mg/dl and levels greater than 90–100
mg/dl or signs and symptoms of end-organ
damage are usually indicative of lethal levels.
With levels this high, hemodialysis should be
initiated. Aspirin levels may start out low and
become toxic within 24 h depending on half-life
and elimination. Absorption can continue for
up to 24 h because of delayed dissolving of
tablets or formation of gastric concretions
(movable intraluminal mass of pills).
738
Urine ph and specific gravity may be useful.
Close monitoring of acid–base status is
essential. Electrocardiogram (ECG) monitoring,
serial arterial blood gases (ABGs), serum
electrolytes, glucose, BUN, and creatinine levels
should be monitored every 4–6 h. Liver
function tests should be monitored as needed.
Monitoring and diagnostic testing for NSAID
overdose is the same as salicylates. Pregnancy
testing should be completed in all women of
childbearing age.
Antidotes/binding agents/treatment
For both ASA and NSAID overdose, GI
decontamination may be performed with
activated charcoal if time of ingestion is known.
Repeated doses of charcoal with rising levels
may be needed with sustained-release formulas
along with whole-bowel decontamination
because of delayed absorption and gastric
concretion. Endoscopy with gastric lavage has
also been utilized in cases of increasing levels.
Hemodialysis may be necessary in cases where
serum levels are more than 100 mg/dl or with
severe and progressive clinical deterioration
that is unresponsive to urine alkaline diuresis;
referral to a renal consultant should be made
early.
Initial fluid management should be D5NS or
D5W with 1 ampule (50 mEq) of sodium
bicarbonate, with 1–3 l given within the first 2 h
if levels are over 30 mg/dl. The goal is to
739
alkalinize the urine to a pH > 7.5 and urinary
output of 2–4 ml/kg/h. Salicylate removal is
increased by alkalization of the urine. CNS
hypoglycemia can occur despite normal serum
blood glucoses and blood glucose monitoring
should be instituted. Treatment with D50 may
be needed in patients with altered mental status
and CNS symptoms.
Supportive measures for airway and circulation
should be instituted for coma and seizures and
if profound organ dysfunction occurs.
Ventilator support with positive end-expiratory
pressure should be utilized in cases of
noncardiac pulmonary edema. Diuretics are
ineffective.
Clinical Pearls
Anion gap acidosis is common. See chapter
summary for analysis of metabolic analysis of
acid–base disorders (see mnemonic for
“MUDPILES”). Tinnitus and hearing loss are
the most common symptoms of ASA
overdose.
Methemoglobin
Drug overview
Methemoglobin is an abnormal hemoglobin
state in which a part of the iron of
740
unoxygenated hemoglobin is in the ferric state
instead of the ferrous state; thus, it is unable to
carry oxygen or carbon dioxide. The presence of
methemoglobin shifts the oxygen dissociation
curve to the left, which increases the affinity of
the remaining hemoglobin to oxygen, making
hemoglobin less capable of releasing oxygen to
the tissues. Methemoglobin may be acquired or
congenital. The acquired form is caused by
exposure to toxins or drugs that oxidize ferrous
iron. Congenital forms are usually caused by
hemoglobin M or NADH methemoglobin
reductase
enzyme
system.
Normal
methemoglobin levels are 1% of total
hemoglobin.
The most common drugs that cause
methemoglobin elevations are local anesthetics
such as benzocaine, which may be present in
many OTC topical medications. Other drugs,
such as nitrates, sulfonamide antibiotics,
benzene derivatives, dinitrophenol (which is an
industrial chemical used by body builders for
rapid weight loss), methanol, methylene blue,
mothballs, pyridium, phenytonin, silver nitrate,
nitrophenol, toluidine, and chlorates may not
be as common. Use of Dapson (an anti-infective
agent used in the treatment of leprosy and
pneumocystis) has been associated with 42% of
cases noted (Skold and Klein, 2013).
Most causes of this clinical condition are due to
adverse medication reactions or illegal
741
recreational abuse of amyl nitrate (called
poppers). Common street names are rush,
snappers, or liquid gold. The drug is usually
inhaled and gives the user a burst of energy
along with a muscle relaxant and vasodilating
effect. Amyl nitrate is also the antidote for
cyanide poisoning. Death can occur in
untreated cases when methemoglobin levels
exceed 70%. Normal methemoglobin levels are
less than 2% but can also be elevated in
cigarette smokers. Levels at 15–20% can cause
symptoms of cyanosis but the patient is
generally asymptomatic.
Symptoms of overdose
Symptoms are related to decreased oxygen
delivery
to
cellular
tissue.
Cyanosis,
tachycardia, and tachypnea are common.
Cyanosis occurs when levels exceed 1.5 g/dl,
generally represented by a chocolate hue
instead of the common blue of cyanosis, seen in
the blood and tissue. Cardiac dysrhythmias can
occur in severe poisoning. Hypotension can
occur in the case of methemoglobin with the
use of nitrates. Lethargy, confusion, seizures,
and syncope may also occur. There have been
reports of cardiac arrest and myocardial
infarction with high methemoglobin levels.
Diagnostic testing and monitoring
ABGs and Methemoglobin levels should be
measured with the use of a cooximeter as
742
calculated oxygen saturation levels and pulse
oximetry values are usually not accurate. Serum
glucose-6-phosphate dehydrogenase (G6PD)
determination can be done to ascertain the
etiology of methemoglobinemia poisoning.
Serum G6PD deficiency can worsen with
administration of methemoglobinemia-causing
drugs. Metabolic panel and assessment of anion
gap acidosis are needed. A complete blood
count (CBC) with peripheral smear and
haptoglobin levels should be completed to
assess for hemolysis.
Antidotes/binding agents/treatment
Treatment
is
supportive.
Oxygen
supplementation is usually needed by 100%
non-rebreather face mask. Intubation may be
needed. Activated charcoal (1–2 g/kg) can be
used if a substantial dose or long-acting drug
that causes Methemoglobin has been given such
as Dapsone (Berlin et al., 1985). The use of
methylene blue may be needed depending on
Methemoglobin levels. Treatment is usually
started if Methemoglobin levels are 30% in an
asymptomatic patient or lower in symptomatic
patients or patients with anemia or cardiac
disease. The dose is 1–2 mg/kg IV and may be
repeated in 1 h. Methylene blue converts the
Methemoglobin in red cells to hemoglobin
(Plotkin et al., 1997). In patients with G6PD
deficiency, the use of methylene blue may
743
aggravate Methemoglobinemia and precipitate
hemolytic anemia (Mansouri and Lurie, 1993).
Clinical Pearls
Gyromitra mushrooms are found in the
northern hemisphere and can cause
hemolysis, seizures, and elevated
Methemoglobin levels. This mushroom is
usually poisonous when raw. Treatment is
with methylene blue. It is common for
patients to present with normal arterial PO2
accompanied by cyanosis (Levine et al.,
2011).
Cautious use of methylene blue is advised in
patients who are receiving selective serotonin
reuptake inhibitors (SSRIs) such as Prozac
and Cymbalta due to the increased risk of
serotonin syndrome in these patients.
Methylene blue inhibits the action of
monoamine oxidase A (MAO), which breaks
down serotonin. In patients receiving SSRIs,
this causes serotonin to rise, leading to
serotonin syndrome. Symptoms include
mental status changes, twitching, hypertonia,
myoclonus, hypertension, high fever, and
hyperactivity (Lowes, 2011) (see Table 13.1).
Table 13.1 Methemoglobin levels and
associated symptoms.
744
Adapted from Harris (2006). © Elsevier.
Concentration Percentage Symptoms
of
of total
methemoglobin hemoglobin*
(g/dl)
<1.5
<10
None
1.5–3.0
10–20
Cyanosis
3.0–4.5
20–30
Anxiety,
lightheadedness,
headache,
tachycardia
4.5–7.5
30–50
Fatigue,
confusion
dizziness,
tachypnea,
increased
tachycardia
7.5–10.5
50–70
Coma, seizures,
arrhythmias,
Acidosis
>10.5
>0
Death
Patients with lower HG levels may experience
more severe symptoms.
*Assumes HG = 15 g/dl.
745
Iron
Drug overview
Iron is generally used in the treatment of
anemia and is an ingredient in prenatal
vitamins. It is a common leading fatal cause of
poisoning in children. Iron has a direct
corrosive effect on tissue and may cause acute
hemorrhage. Ingestion of 60 mg/kg is generally
considered lethal. Ingestions of less than 40
mg/kg of elemental iron do not typically
produce toxic symptoms. Iron is absorbed in
the small bowel and converted into a ferric
state. It combines with ferritin to form
complexes in the intestinal mucosa. Normal
levels are 50–150 μg/dl. In cases of overdose,
transferrin becomes saturated and excess iron
exists as free ferric ions. These ions disrupt
oxidative phosphorylation and catalyze the
formation of oxygen free radicals, which leads
to lipid degradation and cell death. Other
effects are increased capillary permeability and
venodilation, which causes a shift to anerobic
metabolism through mitochondrial dysfunction
and production of hydrogen ions. Peak iron
levels are seen within 4–6 h but may be delayed
in sustained-release formulas.
Symptoms of overdose
Damage to GI mucosa causes massive volume
depletion and fluid losses. Metabolic acidosis,
massive vasodilation, increased capillary
746
permeability, and myocardial dysfunction may
develop. Hepatic failure and necrosis may result
from the formation of free radicals.
Coagulopathy develops from inhibition of
coagulation factors by iron, and later from
hepatic failure.
Iron poisoning usually involves initial corrosive
effects in the GI system followed by resolution
of most GI symptoms. Progressive metabolic
acidosis may be present in lab values. Patients
may then enter into the third stage (6–48 h),
which is progressive shock. This is caused from
direct cytotoxic effects of the iron. In this stage,
there may be an abrupt worsening of symptoms
that lead to cardiovascular collapse, coma,
coagulopathy, liver failure, and death. The need
for
aggressive
interventions
including
hemodialysis and hemodynamic support is
greatest in this stage.
Diagnostic testing and monitoring
Diagnosis is based on history of exposure,
vomiting, diarrhea, bleeding, and hypotension.
It is possible to see radiopaque pills on X-ray.
Elevated serum white blood cell (WBC) and
glucose is also common. Total serum iron levels
should be trended. Toxic dose is frequently seen
with levels higher than 450–500 μg/dl; levels
higher than 800 μg/dl are associated with
severe poisoning. Repeat serum levels should
be obtained within 6–8 h of ingestion to check
for sustained-release forms of medication. CBC,
747
extended metabolic panel, ABGs, LFTs,
prothrombin time/partial thromboplastin time
(PT/PTT), and INR should be trended.
Conservative management is usually done for
levels less than 500 μg/dl. Levels greater than
1000 μg/dl are associated with significant
morbidity.
Antidotes/binding agents/treatment
Chelation therapy is used to treat iron overdose.
Gastric lavage, activated charcoal, and ipecac
syrup are not effective. Whole-bowel irrigation
has been shown to be effective in instances of
visable opacities found on abdominal X-rays.
Iron is radiopaque, but X-rays can also be
negative despite significant toxicity (Hunter
and Taljanovic, 2003). Deferoxamine (DFO) is
used for iron overdose. It binds free iron and
converts it to ferrioxamine. It readily crosses
the cell membrane and removes iron from cells.
Initial infusion begins at 15 mg/kg/h to a
maximum dose of 6 g regardless of weight. Use
of higher doses over a shorter duration is the
preferred method. Acute renal failure and
hypotension can occur with the use of DFO and
chemistries should be monitored. There have
also been instances of adult respiratory distress
syndrome (ARDS) occurring with infusions
lasting for more than 24 h. Rusty-red urine
during treatment of DFO is common but may
not occur. Discontinuation of therapy is based
on resolution of clinical symptoms and acidosis.
748
Clinical Pearls
A normal iron level does not exclude toxicity.
Significant signs and symptoms of toxicity
have been seen in patients with levels less
than 350 μg/dl. Measuring levels of total
iron-binding capacity (TIBC) is not useful in
the management of these patients. TIBC
levels are usually falsely elevated in the
presence of high serum iron levels and are
neither sensitive nor specific (Siff, Meldon,
and Tomassoni, 1999).
Drugs of abuse
Overview
The use of illicit drugs, including OTC and
prescription drugs, remains a large problem
both in urban and suburban health centers.
Frequent drug abusers tend to mix medications
with alcohol and frequently obtain prescription
drug opiates from multiple physicians, friends,
or purchase them illegally (Lessenger and
Feinberg, 2008). Complications that can arise
from
these
drugs
are
cardiovascular
compromise,
thoracic
complications,
neurological insult, infections, and kidney
failure.
749
At times, the unavailability of an illicit drug of
choice results in the substitution of prescription
or OTC drugs. Common drugs of abuse are
crack cocaine, Ritalin, methamphetamine
derivatives,
heroin,
and
other
opiate
derivatives. Complications may include acute
aortic dissection or spinal infarct from the
sympathomimetic effect of cocaine to acute
lung injury from inhalation of crack or other
substances (Gotway et al., 2002).
Symptoms of overdose
If the route used is injection, infection of any
organ or tissue is possible with subsequent
abscess formation. Rapid absorption occurs
with both inhalation (smoking) and IV injection
and lasts for around 30 min. Because of these
effects, cocaine is most addictive by these
routes. Rapid peak concentrations occur in the
brain, and behavioral and psychological effects
have a shorter duration of action. Snorting
cocaine produces a longer duration of action
over
several
hours.
Specific
thoracic
complications that can occur from illicit drug
use are pneumonia, pulmonary hemorrhage,
emphysema, cardiogenic and noncardiogenic
pulmonary edema, acute lung injury, aspiration
pneumonia,
septic
embolization,
and
talc-induced lung disease. Rhabdomyolysis,
hypothermia or hyperthermia, and seizures are
common (Gotway et al., 2002).
750
Diagnostic testing
General
testing
should
include
ASA,
acetaminophen, and standard urine drug panels
that include methadone testing. Alcohol levels
should also be obtained. Monitoring of airway
and continuous and 12-lead ECG monitoring is
warranted. CBC, extended lytes, troponin or
creatine phosphokinase (CPK) levels, and ABGs
should be monitored. False positives for opioids
can occur from dextromethorphan (DMX),
quinine, quinolones, rifamptin, poppy seeds
and oil, and verapamil. False negatives can
occur from low doses of semisynthetic and
synthetic opioids and patients with rapid
metabolism (McBane and Weigle, 2010).
Clinical Pearls
Sending blood or urine samples to toxicology
centers is not feasible in many cases,
especially if no criminal activity has been
committed. There are also many designer
and street-level drugs for which testing is not
available. The most important information is
history and physical assessment.
751
Benzodiazepines
Drug overview
These agents include lorazepam, Xanax,
Valium,
flurazapam,
oxazepam,
and
clonazepam.
These
drugs
are
highly
protein-bound and may take longer to disperse
in obese individuals. They are usually
prescribed for their antianxiety, sedative, or
antispasmodic
effects.
Rohypnol
(flunitrazepam) is commonly known as the
“date rape drug.” It is rapid-acting and causes
significant CNS depression within 30 min.
Rohypnol has a very slow elimination and
prolonged coma is common. It is not detectable
on routine drug screens but can be tested for
specifically at designated labs. Benzodiazepines
enhance the action of the inhibitory transmitter
gamma-aminobutyric acid (GABA). This causes
decreased spinal reflexes and depression of the
reticular-activating system. This in turn can
cause coma and respiratory arrest in overdose
situations.
Symptoms of overdose
CNS depression and respiratory arrest are the
most common symptoms of overdose. Ataxia
can be present. Hypotension is uncommon.
Death is usually uncommon with older forms of
benzodiazepines but more common with the
shorter-acting more potent forms. Toxic effects
are magnified when drugs are combined with
752
other CNS depressants such as barbiturates or
alcohol.
Diagnostic testing and monitoring
Urine drug toxicity screen will be positive for
benzodiazepines. They can be detected in the
urine for 2–7 days.
Antidotes/binding agents/treatments
Charcoal can be given in acute ingestions within
the hour and care must be taken to avoid
aspiration risk. Treatment of benzodiazepine
overdose is supportive. IV infusion of
crystalloids for hypotension is used. Flumazenil
can be given at 0.2 mg IV for one dose.
Additional doses can be given at 1 min intervals
if needed for a total dose of 1 mg. In cases of
chronic use of benzodiazepines and acute
overdose,
use
of
flumazenil
is
not
recommended due to the risk of precipitating
seizures. In the case of coingestions of certain
drugs such as cocaine and amphetamines,
benzodiazepine can be protective and their
effects should not be reversed. If respiratory
depression is present, the airway should be
supported.
753
Clinical Pearls
Certain drugs such as Ativan (IV formula)
and Valium contain a dilutent that contains
propylene glycol (PG) and can cause
metabolic acidosis with anion and osmolar
gap if given in significant quantities. Since
the dose is patient-specific, some patients
develop complications at lower doses than
others (Arbour, 2003). Drugs such as
Rohypnol will not show up in a standard
toxicology screen for benzodiazepines.
Testing for Rohypnol is commonly done in
toxicology kits for sexual assault. Patients can
develop acute withdrawal after cessation of
chronic benzodiazepine use. Symptoms are
similar to acute alcohol withdrawal and
include hypertension, tachycardia, acute
confusion, seizures, and hyperactivity.
Opiods
Drug overview
Opioids are a general group of drugs classified
as narcotics. They are the second leading cause
of accidental death. Emergency room visits for
opioid abuse have doubled from 2004 to 2008
and treatment program admissions increased
400% between 1998 and 2008 (Okie, 2010).
Narcotics are available by both prescriptions
754
such as methadone, morphine, Percocet,
oxycodone, and dilaudid and illicit drugs such
as heroin. DMX, an opioid derivative, has
potent antitussive effects but no analgesic or
addictive properties. At high doses, it is
classified as a hallucinogen and may produce
dissociative general anesthetic similar to
ketamine and phencyclidine (PCP). If
consumed in low recreational doses between
100 and 200 mg, it has a euphoric effect. With
moderate doses around 400 mg it has an
increased euphoric effect with hallucinations
and at very high doses of 700–800 mg, it
produces profound alterations in consciousness
and temporary psychosis. Tramadol is a
centrally acting synthetic analog of codeine
used as an analgesic agent. It also inhibits the
reuptake of norepinephrine and serotonin and
has weak opioid receptor antagonism. It is
generally a prescriptive drug that is used for
moderate to severe pain and is thought to have
less addiction potential than other opioid pain
relievers. It can cause physical and
psychological depression.
Symptoms of overdose
The major symptoms seen in overdose are
respiratory depression and hypoxia, which can
lead to the development of noncardiogenic
pulmonary edema. This is frequently observed
at autopsy for patients who do not receive
treatment and are found deceased. The lungs
755
may be three times the normal size. Frequently,
these patients are found with a “foam cone”
present on their faces as evidence of their acute
pulmonary edema. The mechanism is thought
to be from hypoxic-induced stress pulmonary
capillary fluid leak. Diuresis does not help in
these situations. Frequently seen are miosis,
CNS depression, hypotension, bradycardia,
hypothermia, and slow gastric transit times.
Seizures can also be induced by certain opioids
such
as
fentanyl,
meperidine,
and
propoxyphene. Tramadol overdose in large
amounts can cause convulsions and seizures
with respiratory depression, nausea, vomiting,
and tachycardia observed due to the
sympathomimetic effect.
Diagnostic testing and monitoring
Urine testing is used for opiates/opioids. False
positives in urine for opioids can occur with
prior ingestion of DMX, papaverine, poppy
seeds, quinine, quinolones, rifampin, and
verapamil. Opioids/opiates are usually detected
in the urine for 2–3 days. Prolonged monitoring
of opioid levels in sustained-release derivatives
may be necessary. CBC, chemistries, ABGs, and
chest X-rays should be monitored. Aspiration is
a frequent complication. Anoxic brain injury
can occur in the setting of profound hypoxic
states. Compartment syndrome and subsequent
rhabdomyolysis can develop from prolonged
immobility (Boyer, 2012).
756
Antidotes/binding agents/treatment
Treatment is to support the airway, ventilation,
and oxygenation. Charcoal may be useful. If
sustained-release formulations are suspected,
cathartics should be administered. Naloxone
0.4 mg IV is initially used and this can be
repeated every 2–3 min. Patients who respond
to naloxone may require a continuous drip.
Drips are usually mixed as 4 mg in 250 ml and
started at a rate of 0.4 mg/h. Drips can be
titrated up to maximum dose of 10 μg/kg/min.
Oxygen administration, IV access, ECG
monitoring, and administration of IV
crystalloid infusion with use of vasopressors
may be required. Tramadol treatment should
begin with benzodiazapines. Propoxyphene can
cause dose-dependent widening of the QRS
complex, which is similar to TCA overdose. This
QRS widening affects the fast sodium channels
in the cardiac conduction system. Treatment
can be managed with sodium bicarbonate 1–2
mEq/kg intravenous push (IVP) and repeated
as needed to maintain a serum pH of 7.45–7.55.
Tramadol overdose may cause tachycardia and
hypertension and naloxone can be less effective
and can cause seizures. Recent data on
tramadol overdose with seizures recommend
treatment of seizures with benzodiazapines and
avoidance of prophylactic treatment with
anticonvulsants (Shadnia et al., 2012).
757
Clinical Pearls
Poppy seeds in food can contain enough
codeine and morphine to produce a positive
drug result. False positives and false
negatives depend on what assays are
conducted within facilities. Body packers can
carry large quantities of illicit drugs such as
heroin and can suffer from leakage of
packages and rapid absorption of large
quantities of opioids. Body cavity searches,
immediate X-rays, computed tomography
(CT) scans, and surgical evaluation may be
needed in patients who have been found to
have drugs hidden in body cavities.
Contrast-enhanced CT scans may be helpful.
X-rays have a sensitivity of 85–90% and false
positive studies may be due to bladder
stones, inspissated stool, or intraabdominal
calcifications (Traub, Hoffman, and Nelson,
2003). Critical care admission,
decontamination with charcoal, and
high-dose continuous infusion of naloxone
may be needed. Surgery may be needed in
the case of retained opioid/herion packages.
There have also been cases of acute liver
failure with tramadol overdose (Pothiawala
and Ponampalam, 2011).
758
Cocaine
Drug overview
Cocaine is a sympathomimetic and local
anesthetic. Cocaine promotes the release of the
neurotransmitters
dopamine
and
norepinephrine while also blocking the
reuptake in the central and sympathetic
nervous system. This effect produces a powerful
euphoric state. Psychologic and physiologic
tolerance develops after the first dose.
Forms of cocaine include crack and freebase
cocaine. Cocaine is water-soluble and can be
absorbed through any mucous membrane.
Freebase cocaine is preferred for smoking and
is made by dissolving cocaine salts in an
aqueous alkaline solution and extracting the
freebase solution with a solvent like ether.
Crack is a freebase form of cocaine that is made
by combining sodium bicarbonate (baking
soda) to create an aqueous alkaline solution and
is then dried out or cooked and formed into
“rocks” that are smoked. Cocaine is metabolized
by liver esterases, plasma cholinesterase, and
nonenzymatic
hydrolysis.
Patients
with
impaired pseudocholinesterase may be at
greater risk for toxicity. Toxic dose is highly
variable. A typical “line” of cocaine contains
20–30 mg or more with assorted additives. A
pellet or rock of crack cocaine usually contains
100–150 mg of cocaine with additives.
Ingestion of more than 1 g is usually fatal.
759
Clinical effects are related to the profound
vasoconstriction and hypertension that occur.
These are caused from the inhibition of
catecholamine
reuptake
and
decreased
production of the vasodilator nitric oxide.
Inhalation or IV use results in euphoric
response within 3–5 min. Peak cardiovascular
effects occur within the first 8–12 min and last
for around 30 min. Cocaine snorting effects
occur within the first 15–20 min, peak within
20–40 min, and can last for several hours.
Initial euphoria is usually followed by anxiety,
delirium, psychosis, muscle rigidity, and
seizures. Seizures are usually brief in duration.
If status epilepticus occurs, continued drug
absorption should be suspected as in ruptured
cocaine bags in the GI tract. Packet ingestion
effects can be markedly prolonged and lead to
death (DeMaria and Weinkauf, 2011).
Symptoms of overdose
Patients with severe toxicity may develop
clonus, seizures, and malignant hyperthermia.
Tachydysrhythmias and cardiovascular collapse
with acute myocardial infarction due to
coronary vasoconstriction can occur. Pupils
may be dilated. Symptoms of tea-colored urine
should prompt examination of CPK levels for
the presence of rhabdomyolysis. Flaccid
paralysis and spinal cord infarction may also
occur due to the extreme vasoconstriction that
can occur with cocaine use. Bronchospasm,
760
pulmonary hemorrhage, and pulmonary
infarction are also possible (DeMaria and
Weinkauf, 2011).
A syndrome called crack cocaine lung can occur
which presents as acute lung injury due to the
decreased blood flow and oxygen caused from
the smoke inhalation of this drug. This presents
as cardiogenic and noncardiogenic pulmonary
edema. Signs and symptoms of dyspnea, chest
pain, cough, and fever typically occur within 48
h of heavy crack smoking.
Chest X-ray results may show abnormal signs
such as hyperinflation, increased vascular
markings, and tree in bud sign on CT scan.
Laboratory
abnormalities
can
include
hypokalemia, leukocytosis, and hyperglycemia
(Devlin and Henry, 2008). Agranulocytosis may
occur due to the adulterants that are combined
with cocaine. Levamisole is an anthelminthic
and immunomodulator that belongs to a class
of synthetic imidazothiazole derivatives. It is
currently used in veterinary medicine as a
dewormer in livestock. Levamisole has been
found by the US drug enforcement to be
present in the majority of cocaine samples
seized. It has been implicated as a suspected
etiological agent in rare cases of agranulocytosis
following
cocaine
ingestion.
Certain
morphologic findings on bone marrow biopsy
in the cases of unexplained agranulocytosis and
cocaine use have been found including
761
circulating
plasmacytoid
lymphocytes,
increased bone marrow plasma cells, and mild
megakaryocytic hyperplasia (Czuchlewski et al.,
2010). Other complications seen with
levamisole use are vasculopathy syndrome,
autoimmune mediated neutropenia, cutanous
vascular
complications,
and
leukoencephalopathy. There are case reports of
treatment with granulocyte colony-stimulating
factor (GCSF) in severe cases (Buchanan and
Lavonas, 2012).
Diagnostic testing and monitoring
Patients usually have hemodynamic instability
with toxic doses of cocaine and commonly
develop acute lung injury, which requires
intubation. Urine usually stays positive for 3
days but a negative result does not rule out
toxicity as urine levels can be very low within
the first few hours. Patients should have IV
access, receive cardiac monitoring, and be
watched for signs and symptoms of seizures. If
seizures occur, treatment should consist of
protection of the airway and intubation if
needed along with benzodiazepine treatment of
Ativan 1–4 mg IVP or Versed 2–5 mg IVP.
Treatment with phenytoin is not effective for
seizures and should be avoided. Propofol
infusion and dexmedetomidine (Precedex)
infusions are also safe to use for sedation and
anxiety. Ketamine should be avoided due to its
sympathomimetic properties and the potential
762
to precipitate myocardial depression in the
setting of limited cathecholamine reserves.
Status epileticus should be managed with
short-acting barbitutes and general anesthesia
can be employed in refractory cases.
Succinylcholine should not be used because it
may increase muscle contraction, and
exacerbate hypokalemia and hyperthermia.
Rocuronium (0.6 mg/kg) and Vecuronium
(0.08–0.1 mg/kg) are the drugs of choice that
can be used for paralytic agents (DeMaria and
Weinkauf, 2011).
In the case of malignant hyperthermia,
paralysis and cooling is the treatment of choice.
CBC and complete electrolyte profile, blood,
urea, nitrogen, and creatinine should be tested.
CPK levels along with chest X-ray should also
be monitored. Cardiac parameters and12-lead
ECG should be done in patients with critical
illness and toxicity as the profound
vasoconstriction of cocaine/crack use can
frequently cause myocardial infarction from
severe coronary vasospasm. Thiamine, folate,
and multivitamins should also be administered
as alcohol abuse is commonly seen with
cocaine/crack use.
Tachyarrhymias and hypertension can be
treated with CCBs (5–20 mg diltizem) IVP
followed by an infusion at 5–15 mg/h, alpha
adrenergic blockers such as phentolamine
(treatment of adrenergic sympathetic excess) in
763
doses of 1–2 mg/dose. IV vasodilators such as
nitroglycerin drip or hydralazine 10–20 mg
every 4 h can also be used to alleviate signs and
symptoms of coronary vasospam and
hypertension.
Hypotension
should
be
aggressively treated with fluid hydration.
Beta-adrenergic blockers such as labetalol,
metroprolol, esmolol, and propanolol should
not be used because they may worsen coronary
spasm. Unopposed alpha-mediated peripheral
vasoconstriction
with
nonselective
beta
blockers is potentially catastrophic. Labetalol,
which has both alpha and beta-blockage
properties, has been shown to lower blood
pressure but does not improve coronary blood
flow. Dexmedetomidine has been postulated to
alleviate coronary vasospasm via a central
sympatholysis (Schwartz, Rezkalla, and Kloner,
2010). If signs and symptoms of intestinal
obstruction are present, immediate surgical
intervention is needed. If packets of cocaine are
swallowed
for
diversion
of
drug,
life-threatening injury can occur if the package
leaks. Positive urine tests for cocaine can occur
with the use of the coco leaf tea.
Antidotes/binding agents/treatment
There is no specific antidote for cocaine
overdose. Charcoal is usually ineffective.
Dialysis is ineffective and acidification of the
urine may aggravate myoglobinuric renal
failure.
764
Clinical Pearls
It is possible to see symptoms of “crack
dancing” or “twisted mouth,” which is acute
dyskinesia that presents as repetitive eye
blinking, lip smacking, and involuntary
movements and contractions of the arms and
legs in some patients. This usually resolves
within a few hours to a few days. Body
temperature above 104–105 °F can be
life-threatening and patients should be
cooled immediately with external or internal
cooling devices. Substances that are added to
cocaine before it is sold on the street can
include talc, lactose, mannitol, sucrose,
caffeine, heroin, phencyclidine, lidocaine,
procaine, and strychnine. Some of these
substances can also cause toxicity. The
combined use of cocaine and ethanol forms
cocaethylene in the liver, a substance that
intensifies and lengthens cocaine’s euphoric
effects while possibly increasing the risk of
sudden death (Farre et al., 1997).
Amphetamines
Drug overview
Amphetamines and other similar drugs activate
the sympathetic nervous system. The four
mechanisms involved are catecholamine release
765
from neurons, inhibition of monoamine
neurotransmitter uptake of catecholamines,
binding
to
extracellular
catecholamine
receptors, and inhibition of monoamine
oxidase. Amphetamines are capable of altering
neurotransmitter release. Each can affect
different chemicals in the brain and have
multiple effects. Some stimulant actions such as
methylenedioxymethamphetamine
(MDMA)
(ecstasy) and bupropion (Wellbutrin) have not
been fully explained. Amphetamines can be
used to treat certain disorders such as
narcolepsy and attention deficit disorders.
Amphetamines can be ingested as an illicit drug
such as methamphetamine, Ecstasy, and
lysergic acid diethylamide (LSD). People can
develop “meth mouth,” which is erosion of the
teeth from chronic methamphetamine use.
Amphetamines are generally well absorbed
orally and have a large volume of distribution.
Half-life varies depending on the drug ingested.
Symptoms of overdose
Generally, symptoms have to do with CNS
overstimulation. Symptoms of euphoria,
agitation, aggression, anxiety, hallucinations,
seizures, coma, hyperthermia, all forms of
cardiac dysrhythmias, myocardial infarction
from vasospasm, extreme muscular rigidity and
hyperactivity, mydrosis, and hypertension can
lead to acute hemorrhagic intracranial bleeding.
766
Rhabdomyolysis with acute renal failure is
possible.
Diagnostic testing and monitoring
Diagnosis is usually based on history.
Amphetamines are usually detected in the urine
for 2–3 days. Suspicion should be high for any
patient that comes in with seizures, muscular
rigidity, fever, and rhabdomyolosis. Drug urine
toxicology screen should be sent for
amphetamines. There can be some cross
reactivity to other substances such as
pseudoephedrine and its derivatives, including
OTC antihistamines. Most drug screens for
amphetamines may not pick up toxicology for
Ecstasy, which may need to be a specific
separate test. Check with the hospital lab
department or Poison Control Center.
Antidotes/binding agents/treatments
Treatment is supportive. Charcoal can be given
if treatment is sought within 2 h of ingestion.
Patients may need aggressive cooling, fluids,
support of airway, cardiac monitoring, and
treatment of seizures and muscle rigidity with
benzodiazepines. Antipyretics have no use in
therapy for this type of hyperthermia, as the
action is a lowering of the hypothalamic set
point, which is not relevant in amphetamine
overdose (Eyer and Ziker, 2007). If treatment is
needed for hypertension, nitroprusside or
nitroglycerin can be used. Esmolol or
767
short-acting beta blockers can be used for
tachyarrhythmias. Generally, the effects of
amphetamines are not longlasting and few act
for longer than 24 h. Dialysis and
hemoperfusion
are
ineffective
in
the
elimination of amphetamines. Continuous
cardiac monitoring, 12-lead ECG, CBC,
complete metabolic panel, CPK, and cardiac
isotopes
with
troponin-I
levels
are
recommended.
Clinical Pearls
Methamphetamine use is endemic to some
rural areas. It can be smoked, snorted,
injected, or taken orally. It is relatively
cheaper than other drugs of abuse. It is
usually used in a binge and crash pattern and
has a longer duration of effect than cocaine.
Smoking produces a longlasting high, and
50% of the drug is removed from the body
within 12 h as opposed to cocaine, which is
gone within 1 h. Long-term use can lead to
addiction with both psychological and
long-term molecular changes in the brain.
Psychotic changes in behavior along with
hallucinations are common. Designer
amphetamines such as Ecstasy have
serotonergic activity and in the setting of
other SSRIs or TCAs can produce serotonin
syndrome (Meehan, Bryant, and Aks, 2010).
768
False positive urine tests can occur with the
use of poppy seeds and ephedrine (Neerman
and Uzoegwu, 2010).
Phencyclidine
Drug overview
PCP is a dissociative anesthetic with
hallucinogenic properties. Phencyclidine can
cause extreme agitation and aggressive
behavior. Patients may need to be chemically
sedated and ventilated to handle behavioral
issues and injuries.
This
agent
primarily
acts
by
N-methyl-d-aspartate
(NMDA)
receptor
antagonism
and
modulating
serotonin
antagonism. It is structurally related to
ketamine (Meehan, Bryant, and Aks, 2010).
PCP is readily absorbed by all routes, highly
protein-bound, and metabolized in the liver. It
has a rapid onset of action, effects last 6–24 h,
and alterations in perception can occur for up
to 3 days. It is usually detected in the urine for
up to 2 weeks and in some instances up to 1
month.
Symptoms of overdose
PCP causes a dissociative state with loss of
reality. Perceptions are altered and visual and
769
auditory hallucinations are frequent. Patients
can appear intoxicated, agitated, calm, or
comatose. Multidirectional nystagmus may be
present. Hypertension, tachycardia, and
hyperthermia may be present. Behavior may be
violent and unpredictable. Muscle twitching,
rigidity, and neuromuscular hyperactivity can
occur. Rhabdomyolysis can occur from
neuromuscular hyperactivity. Patients rarely
present to medical providers and usually
present due to coingestion of other substances
or from trauma experienced from the effects of
the drugs.
Diagnostic testing and monitoring
Vital signs, ECG monitoring, and tests to rule
out other neurological conditions should be
done. Drug screening for PCP, blood glucose
testing, CBC, CPK, and complete metabolic
panel should be done. Physical and chemical
restraints may be needed for violent and
aggressive behavior. Complications can occur
including aspiration pneumonia, multisystem
organ failure from hyperthermia, trauma, and
extreme hyponatremia from water intoxication.
Antidotes/binding agents/treatments
Activated charcoal can be given within the first
1–2 h. Care is supportive. Advanced life support
measures should be instituted if needed such as
intubation,
chemical
paralysis,
cooling
measures for hyperthermia, and aggressive
770
fluid resuscitation. Benzodiazepines can be
given for acute psychosis. Monitoring of airway,
oxygen saturation, and end tidal CO2
monitoring must be done.
Clinical Pearls
Use of large doses of DMX can cause a false
PCP result in urine. Typically, PCP is added
to other drugs for smoking or ingestion to
enhance effects (Neerman and Uzoegwu,
2010).
Barbituates
Drug overview
Barbituates are a class of sedative–hypnotic
and anticonvulsive drugs. Examples include
phenobarbital,
pentobarbital,
thiopental,
butalbital, secobarbital, chloral hydrate,
zolpidem, and others drugs that have mixed
properties. Serum concentration levels can be
measured for certain barbiturates. Tolerance
can develop over time with multiple drug
ingestions. Barbiturates are used to treat
seizures, anxiety, withdrawal symptoms,
musculoskeletal disorders, and for anesthesia.
Withdrawal symptoms with abstinence may be
present after chronic use. Chronic toxicity can
develop with insidious signs and symptoms
771
such as confusion, sedation, nystagmus, and
ataxia.
Most barbiturates work to either increase
inhibitory tone or decrease excitatory tone.
They may be classified as either short- or
long-acting. They may also be classified as
anticonvulsant,
sedative–hypnotic,
or
anesthetic. Barbiturates bind to barbiturate
receptors in the CNS. This receptor is part of
the GABA-A receptor complex. Binding on this
receptor facilitates GABA neurotransmission,
causing CNS depression. GI absorption is rapid
and effects depend on the lipid solubility of the
substance. Protein binding may be extensive for
some drug forms and drugs such as chloral
hydrate may produce active metabolites and
prolonged elimination. Most drugs are
metabolized in the liver, except baclofen and
chloral hydrate, which are renally excreted.
Symptoms of overdose
Signs and symptoms of CNS depression are
common.
Coma
can
occur
with
thermoregulatory depression in the brain stem
which can cause apnea, hypothermia, and
shock. Respiratory depression and hypotension
can occur. Signs and symptoms of depressed
myocardial activity and skeletal muscle
weakness are common. Symptoms may be
highly variable depending on the barbiturate
ingested.
772
Diagnostic testing and monitoring
Drug
screening
is
recommended
for
barbiturates or specific substances ingested.
Often drug levels must be sent to outside
laboratories and may take up to 4–6 days to
obtain results. Other testing should include
CBC, complete metabolic panel, blood glucose
monitoring, end–tidal CO2 monitoring, ABGs,
and ECG monitoring. Ventilation may be
needed along with IV access and crystalloid
support for hypotension.
Antidotes/binding agents/treatments
Care is supportive. Charcoal may be beneficial
with acute ingestion within 1–2 h but is of little
benefit with chronic ingestion. Vasoactive drugs
can be used if hypotension is present and does
not respond to fluid resuscitation. Naloxone
may reverse CNS depression in patients who
have valproic acid overdose who are not
opioid-tolerant. To enhance elimination of
long-acting barbiturates, infusion of sodium
bicarbonate can be used to alkalinize the urine
to a pH between 7.5 and 8.0. Infusion of 1–2
mEq/kg as a bolus followed by an infusion of 1 l
of D5W with 2–3 ampules of sodium
bicarbonate at 75–100 cc/h can be given.
Hemodialysis is not indicated unless severe
phenobarbital overdose is present with
multisystem organ failure and failure to
respond to other conventional therapies.
773
Clinical Pearls
Most barbituates are usually detected in the
urine for less than 2 days, but up to a week
for phenobarbital. Chloral hydrate overdose
impairs myocardial contractility, shortens the
cardiac refractory period, and sensitizes the
myocardium to catecholamines. This can
cause a variety of cardiac arrhythmias such as
atrial fibrillation, ventricular tachycardias,
and torsades de pointes. Beta blockers are
the drugs of choice for this agent. Overdose
with Ambien can produce drowsiness but
coma and respiratory failure are uncommon.
Hallucinogens
Drug overview
Hallucinogens include LSD and “magic
mushrooms.” Effects and treatment are similar
to PCP intoxication. LSD is usually sold in
single or double squares, blotter paper, gelatin
squares, or other residue powder. Typical doses
range from 25 to 300 μg and massive ingestion
can lead to life-threatening consequences.
Lysergamides are also found in morning glory
seeds and several hundred seeds are required
for a hallucinogenic effect. Magic mushrooms
contain psilocybin. These have psychotropic
properties similar to LSD. Magic mushrooms
774
originate in the United States from the use by
North
American
Indians
in
religious
ceremonies. They can be grown or ordered over
the Internet. Their chemical structure is very
similar to that of LSD and serotonin. Symptoms
of intoxication usually occur within 30–60 min
of ingestion (Meehan, Bryant, and Aks, 2010).
Symptoms include a feeling of euphoria,
agitation, disorientation, and hallucinations.
Bradycardia and hyperthermia may occur.
Symptoms are usually self-limiting. Care is
similar to LSD intoxication.
Symptoms of overdose
Patients rarely present with LSD/mushroom
intoxication but can have auditory and visual
hallucinations along with the symptoms
described earlier. Symptoms generally occur
within 30 min of ingestion. Effects can last up
to 12 h and LSD may be coingested with other
toxins. Patients can also develop hypertension,
tachycardia,
and
hyperthermia.
Mild
methemoglobinemia may be seen with magic
mushrooms. Doses in excess of 14 000 μg can
produce
life-threatening
hyperthermia,
seizures, coagulopathy, and respiratory arrest
(Meehan, Bryant, and Aks, 2010).
Monitoring and treatment
Care is supportive and there is no specific
antidote. CBC, complete metabolic panel, CPK
levels, and glucose monitoring should be
775
completed. ECG monitoring is advised in cases
of large overdose. Hyponatremia may be
present due to extreme dehydration. IV
crystalloids should be given in large doses for
extreme
hyperthermia,
dehydration,
or
rhabdomyolosis. Standard drug testing does not
detect most hallucinogenics.
Clinical Pearls
Salvia divinorum has became a popular
hallucinogenic over the last 5–6 years. It is a
perennial herb found in the Sierra Mazatec
area of Mexico. It acts as a kappa opioid and
serotonergic agonist along with glutamate
antagonism (Ghosh and Ghosh, 2010). It can
be easily purchased over the Internet and is
usually smoked or taken orally. Overdose is
not common but it can be frequently
coingested with other drugs as a
hallucinogenic.
Club drugs/date rape drugs
Drug overview
Ecstasy or MDMA, gamma hydroxybutyrate
(GHB),
Rohypnol
(see
Section
“Benzodiazepines”), ketamine, and DMX are a
general group of drugs that are used to facilitate
rape or are used recreationally in urban and
suburban areas by young adults and teenagers.
776
Ecstasy was patented in 1914 by Merck
Pharmaceuticals as an appetite suppressant,
but was later studied as a psychotherapeutic
drug (DeMaria and Weinkauf, 2011). Ecstasy
structurally
resembles
mescaline
and
amphetamines.
Drug-facilitated rape should be suspected in
any person who appears intoxicated and
confused who also has amnesia and may be
partially clothed or unclothed. Any person who
is admitted to the hospital and has been found
unresponsive in suspicious circumstances
should have a toxicology screen done and if
criminal action has been committed or is
suspected, extra blood should be drawn for
more extensive toxicology. Rape kits may also
need to be completed. Most state rape kits now
include blood work for toxicology to rule out
drug-facilitated sexual assault. If in doubt, err
on the side of caution and draw and process the
kit. If the patient wakes up and remembers that
nothing happened, the kit does not have to be
processed. Most states allow submission of the
kit with a control number for patients who want
to submit anonymously. Ingestion results in
signs and symptoms of confusion, intoxication,
slurred speech, amnesia, unsteady gait, high
fever, tachycardia, euphoria, and high-risk
behaviors. Ecstasy is an amphetamine-MDMA
used commonly at clubs and is usually taken in
conjunction with alcohol. Ecstasy is usually not
physically addictive.
777
Symptoms of overdose
Effects are generally seen within 30 min and
last up to 8 h. Use of MDMA produces feelings
of euphoria, and increases energy and
psychomotor drive. It causes an increased
positive mood and sense of closeness with
others. Adverse effects include anxiety and
thought disorders, hypertension, increased
myocardial oxygen demand, jaw clenching,
high-risk sexual behavior, tachyarrhythmias,
seizures, and hyperthermia with acute
dehydration. Myocardial infarction and dilated
cardiomyopathy has been reported (DeMaria
and Weinkauf, 2011). Hyponatremia is common
due to acute water intoxication from excessive
thirst. Increased antidiuretic hormone secretion
from MDMA central effects may worsen
hyponatremia. Neurotoxicity has been reported.
There have been reported cases of liver failure
and cerebral hemorrhage. Long-term use can
cause chronic psychosis in at-risk individuals
and possible neurotoxicity
(Britt
and
McCance-Katz, 2005).
Diagnostic testing and monitoring
Testing should include CBC, serum metabolic
panel, CPK levels, and ECG monitoring. IV
hydration with crystalloids should be given to
correct dehydration. Standard drug toxicology
should be done for coingestion along with
alcohol testing. MDMA is not detected in
regular drug screens unless specifically tested
778
for; contact the laboratory for specific drug
testing coverage.
Antidotes/binding agents/treatments
Care is supportive. Seizures should be treated
with benzodiazepines. Rhabdomyolysis is
common in cases of extreme hyperthermia and
internal cooling devices may be needed. If acute
pill ingestion occurred within 1–2 h, treatment
with activated charcoal in 1 g/kg dose may be
given. The maximum dose is 50 g. There is no
specific antidote or binding agent. In causes of
extreme hyperthermia and rhabdomyolysis,
dantrolene has been used. Dantrolene is a
muscle relaxant that depresses excitation and
contraction coupling in skeletal muscles by
binding ryanodine receptors and decreasing
intracellular calcium concentration (Hall and
Henry, 2006).
Clinical Pearls
Most use of ecstasy is consumed at RAVEs,
which are large-scale dance parties generally
held in urban areas. There is also a higher
likelihood of polysubstance use at these
events. Most common coingestions are with
GHB, ketamine, and flunitrazepam. Common
names for ecstasy are XTC, Adam, X, and E.
Ecstasy is commonly combined with Viagra
779
because of its effect that can cause erectile
dysfunction. Viagra may be abused by the gay
population and may lead to seropositive
human immunideficiency virus (HIV) results
due to unsafe sexual practices (Lessenger and
Feinberg, 2008).
Ketamine
Drug overview
Ketamine produces symptoms similar to PCP
when it is abused. It can be used orally,
intravenously, nasally, or by inhalation. It can
be combined with other drugs. It has a rapid
onset and due to the hallucinogenic effects it is
difficult for the user to resist the attacker if this
is used as a date rape drug. It generally
produces loss of pain perception with little to
no depression of airway reflexes or ventilation.
Ketamine is not physically addictive. It is used
mostly by anesthesiologists for children because
of its analgesic role (Demaria and Weinkauf,
2011). It is also commonly used in veterinary
medicine. Ketamine abuse has risen over the
last decade and is commonly combined with
MDMA.
Ketamine is an NMDA receptor agonist. This
causes
noncompetitive
antagonism
of
glutamate in the CNS. Ketamine binds to the
same receptor site as PCP located on the
780
calcium channel, leading to a blockage of
calcium
flow.
This
decreased
neurotransmission causes altered perception,
memory, and cognition. Blockage of the NDMA
receptor causes feelings of relaxation at low
doses and acute dissociative states and
phychosis with visual hallucinations at higher
doses. Effects of ketamine generally last for 1–3
h, but depending on the amount of the
overdose, effects can be seen for up to 14 h
(DeMaria and Weinkauf, 2011). Ketamine is
eliminated hepatically with small amounts
excreted by the gastric and renal systems. Usual
therapeutic doses are 1–5 mg/kg IV.
Recreational doses are usually much higher
with inhalation doses of 10–250 mg, oral doses
of 40–450 mg, and intramuscular (IM) doses of
10–100 mg. These higher dosages are taken to
try to reach a psychic state known as the
“K-hole” (Britt and McCance-Katz, 2005).
Symptoms of overdose
Vertical and horizontal nystagmus is a key
feature of intoxication that helps to distinguish
ketamine use from other drugs. Severe agitation
and psychosis may also occur (DeMaria and
Weinkauf, 2011). It may be necessary to
intubate and sedate patients using a
benzodiazapine to be able to control aggressive
behavior. Use of Haldol may be necessary
depending on the degree of psychosis. Haldol
can decrease the seizure thresehold. Polydrug
781
use also needs to be considered as most
overdoses with ketamine occur in young adults
who are experimenting with drug use. Patients
may have tonic–clonic movements or seizures.
Because the sympathomimetic system is
triggered, hypertension, tachycardia, and
arrhythmias are common. Ketamine has
generally no effects on the renal or hepatic
system.
Diagnostic testing and monitoring
Care is supportive with maintenance of airway,
breathing, and circulation. Patients may require
ICU level of care to manage their airway,
agitation, and psychosis. CBC, CPK levels,
extended metabolic panel, and ABGs should be
completed. Continuous ECG monitoring should
be done. Hyperthermia and rhabdomyolysis
may occur. General testing is not available for
ketamine levels. Aggressive hydration with
crystalloids may be needed.
Antidotes/binding agents/treatments
There is no specific binding agent or treatment.
For oral ingestion, charcoal can be given within
the first hour. Dialysis or use of bicarbonate is
not helpful.
782
Clinical Pearls
Always run routine drug, alcohol, and other
levels on patients with signs and symptoms
of drug toxicity. In patients with ketamine
overdose, the agitated behavior may fluctuate
between psychosis and catatonia.
Fake marijuana
Drug overview
Use of synthetic marijuana has become
increasingly popular among teens in recent
years. Synthetic marijuana is usually sold as
incense and referred to as K2, Spice, Genie,
smoke, skunk, and zohai (Korioth, 2011). It is
commonly sold in retail shops and over the
Internet. It is a smokable product and
promoted as a cannabis alternative that is not
detectable on conventional drug screens. There
have been some reports of severe effects of
these drugs depending on what they contain. As
of August 2010, there were 1057 reports of
synthetic cannabinoid toxicity across the United
States (Wells and Ott, 2011). Synthetic
canniboids may contain such chemical
compounds as JWH-, CP-, and HU- along with
oleamide, a fatty acid with cannabinoid-like
activity (Every-Palmer, 2011). The primary
effect of these agents is hallucinations, anxiety,
783
and psychosis and they tend to cause
tachycardia and increased blood pressure. This
herbal cocktail can consist of canavalia rosea,
clematis nuciferia, heima salicfolia, and ledum
palustre. When smoked, they produce an
intoxicating effect on the brain very similar to
marijuana. Many of these substances have been
banned, but as soon as they are, more
chemically synthetic compounds are produced
and marketed. Ingestion of these substances is
detected from history as there is no
standardized drug testing (Ernst et al., 2011).
Symptoms
Intoxication may be seen in the acute hospital
settings and can cause significant bradycardia,
psychomotor
agitation,
violence,
and
hallucinations. Four agents may be used in the
making of Illy and they are marijuana (THC),
phencyclidine, formaldehyde, and embalming
fluid (ethyl alcohol). Embalming fluid may
contain methanol, formaldehyde, ethanol, or
ethyl alcohol. Use of Illy or “wet” is popular
among teens and gangs because the marijuana
joints burn more slowly, prolonging the level of
intoxication. Drugs levels may come back
positive for PCP and marijuana.
Diagnostic testing
There is no specific drug test for Illy and
monitoring is based on self-reporting.
Symptoms include psychomotor hyperactivity,
784
hallucinations, and aggressive behavior. Signs
and symptoms clear after 24–36 h depending
on the drugs used. Care is supportive with
monitoring of ECG and vital signs and volume
resuscitation. CBC and extended metabolic
panel should be done. ABGs will determine if
significant metabolic acidosis is present.
Treatment of agitation can be managed with the
use
of
benzodiazepines
or
Haldol
(Modesto-Lowe and Petry, 2001).
Antidote
There is no test or antidote available. Care is
supportive.
Clinical Pearls
Illy may be a common drug used with those
who have gang affiliations. Patients will
usually test positive for marijuana and may
be positive for PCP. Inhalation of
formaldehyde can cause acute onset of
respiratory and mucosal irritation with
difficulty in swallowing and breathing and
metabolic acidosis may or may not be present
due to the use of embalming fluid derivatives.
785
Dextromethorphan
Drug overview
This is a medicine that is used to suppress
cough. DMX overdose occurs when someone
accidentally or intentionally takes more than
the recommended amount. DMX is commonly
abused by 10th–12th graders. DMX is a
synthetically produced substance that is
chemically related to codeine, though it is not
an opiate. Most users of DMX ingest the drug
orally, although some snort the powdered form
of the drug. Some abusers ingest 250–1500 mg
in a single dosage, far more than the
recommended therapeutic dose of 10–20 mg
every
4
h
(Intelligence
Bulletin:
Dextromethorphan, n.d.).
DMX is classified as a nonopiod tussive, the
cytochrome P450, CYP2D6 isoenzyme is
responsible for the conversion of DMX to
dextrorphan; and P450 CYP3A4 and CYP3A5
isoenzymes are responsible for converting DMX
to
3-methoxymorphinan
and
3-hydroxymorphinan. Potential inhibitors of
these isoenzymes could decrease the rate of
DMX elimination if administered concurrently,
while potential inducers could increase the rate
of elimination (Falck et al., 2006).
OTC products that contain DXM often contain
other ingredients such as acetaminophen,
chlorpheniramine, and guaifenesin. Large
786
dosages of acetaminophen can cause liver
damage. Large dosages of chlorpheniramine
can cause tachyarrhythmias, ataxia, seizures,
and coma, and large dosages of guaifenesin can
cause vomiting. First-time users may decide not
to abuse DXM if they experience negative side
effects such as vomiting, which can be
commonly associated with the other ingredients
contained in OTC DXM medications. DXM
abusers can “robo shake,” which is a practice
where they drink a large amount of DXM and
then force themselves to vomit, so they absorb
enough DXM through the stomach lining to get
high while getting rid of the other ingredients.
More experienced abusers use a chemical
procedure to extract the DXM from the other
ingredients contained in cough syrups to avoid
such side effects. This procedure cannot be used
on DXM products sold in nonliquid form. There
are also reports that DMX is used in
combination with Heroin to enhance the effects
of
the
drug
(Intelligence
Bulletin:
Dextromethorphan, n.d.).
Symptoms of overdose
Hallucinations, euphoria, altered state of
consciousness, seizures, syncope, tachycardia,
mydriasis,
hypertension,
vomiting,
and
dissociation to events are typically seen in
overdose. Withdrawal can also occur with abuse
of DMX. Life-threatening effects can occur at
higher
dosages
including
respiratory
787
depression. Most moderate overdosages resolve
spontaneously without serious events but 5% of
those with European ethnicity lack the ability to
metabolize the drug normally, which can lead to
rapid, toxic levels secondary to decreased
metabolism and elimination. Symptoms can be
similar to PCP intoxication (Lessenger and
Feinberg, 2008). DMX can inhibit serotonin
reuptake, which can lead to serotonin
syndrome. Symptoms can generally occur at
doses higher than 10 mg/kg.
Diagnostic testing and monitoring
Blood and urine tests can be done to detect the
drug. Tests are usually sent out from hospitals
and are not usually included on a standard drug
screen. Care of DMX overdose is supportive,
consisting of IV fluids and support of the
airway.
Monitoring
and
testing
for
concommitant drug use and treatment is
needed.
Antidotes
No antidote is available.
Clinical Pearls
DXM use can cause false positives for PCP on
drug screens. DMX can inhibit serotonin
reuptake at the 5-HTA receptors and can lead
788
to serotonin syndrome, especially when other
SSRIs are used (Neerman and Uzoegwu,
2010).
Bath salts
Drug overview
Bath salts are a newer form of chemically
engineered “designer drugs” that have been
popular in Europe for a number of years and
are now being seen in the United States. Poison
Control Centers in the United States reported
6138 calls in 2011 related to bath salt exposure
(American Association of Poison Control
Centers, 2012). These chemical compounds are
usually substances that contain any of the
following substances in various combinations
with other additives that are frequently
changing: mephedrone, synthetic cathinone,
methylone,
methylenedioxypyrovalerone
(MDPV),
methedrone,
and
fluoromethcathinone. Cathinone is a naturally
occurring beta-ketone amphetamine from the
Catha edulis plant (Prosser and Nelson, 2011).
Synthetic cathinones are derivatives of these
drugs. These drugs produce amphetamine-like
effects and are also able to modulate serotonin
levels, which causes psychotic effects. They are
frequently sold on the Internet and advertised
as bath salts. They are sold under names such
789
as Ivory Wave, Vanilla Sky, Snow, and
Hurricane (Smith, Cardile, and Miller, 2011).
Cathinones are similar in structure to ecstasy.
Drugs can be snorted, smoked, taken orally or
rectally, and injected.
Symptoms of overdose/use
Bath salts are commonly coingested with other
drug substances such as marijuana, cocaine,
alcohol, or opiates. Effects of the synthetic
cathinones include increased libido but inability
to perform, increased energy, and a feeling of
euphoria. Adverse and overdose symptoms
include
psychotic
behavior,
aggression,
increased
agitation
and
strength,
hallucinations, nausea, vomiting, diaphoresis,
high fever, and signs and symptoms affecting
the cardiac, neurological, and psychiatric
systems. Acute lung injury and pulmonary
edema have also been reported. The most
common symptom is agitation to severe
psychosis that requires extreme chemical
sedation and restraint. Other cardiovascular
symptoms include acute myocardial infarction,
syncope, and arrhythmias. Symptoms reported
to two regional Poison Control Centers in 2009
and 2010 included agitation, combative
behavior, tachycardia, hallucinations, paranoia,
confusion,
chest
pain,
myoclonus,
hypertension, mydriasis, CPK elevations,
hypokalemia, and blurred vision (Spiller et al.,
2011).
Symptoms
may
mimic
a
790
sympathomimetic toxidrome with associated
neurological symptoms.
Diagnostic testing and monitoring
There is no available standard drug toxicology
test or antidote. Testing is done by using gas
spectrometry or liquid chromatography mass
spectrometry techniques and can be measured
in blood, urine, hair, and stomach contents
(Prosser and Nelson, 2011). Patients should
have CBC, extended chemistries, CPK, ABGs,
chest X-ray, and cardiac enzymes and
continuous ECG monitoring.
Antidotes/binding agents/treatments
Treatment is supportive and focused on
maintaining airway, breathing, and circulation.
For hyperthermia, use of active hypothermic
cooling may be required. Seizures and agitation
can be treated with benzodiazepines. If
psychosis agitation and aggression are
profound, use of intubation with chemical
paralysis may be needed. IV crystalloids should
be given to initially manage hypotension with
use of inotropic agents after adequate volume
resuscitation. Use of propofol may be needed.
Seizures can be treated with Dilantin and
Keppra. Information on withdrawal and
addiction is evolving as not much is known
about this designer class of synthetic cathinone
drugs. There have been reports of anxiety and
depression and reports of up to 50% of users
791
who felt it was addictive (Prosser and Nelson,
2011).
Clinical Pearls
Bath salts are an evolving area of research
and most information is available as case
reports and antidotal evidence. Ingestion of
this substance should be considered in areas
where college age and teenage populations
are numerous or when patients present with
behavior that is not reflective on drug
screens. Some evidence exists that the
psychotic behavior is extreme and patients
are uncontrollable, placing EMS and
health-care providers at risk of significant
injury. All care and precautions should be
maintained. Urine also has a characteristic
“fishy odor,” which has not been explained
but may be due to mephedrone use.
Skeletal muscle relaxants
Drug overview
Skeletal muscle relaxants (SMRs) such as Soma
(carisoprodol), Flexeril (cyclobenzaprine), and
Lioresol (baclofen) are drugs used to treat
muscle spasm and spinal dystonia and
dysreflexia.
They
act
as
simple
sedative–hypnotic agents that produce skeletal
muscle relaxation indirectly. Abuse of muscle
792
relaxants frequently occurs in combination with
other drugs. Soma is frequently used in large
doses as a sexual stimulant when taken with
alcohol. Soma abuse can lead to tolerance,
dependence, and withdrawal. Phenobarbital
has been used successfully in Soma withdrawal
(Boothby, Doering, and Hatton, 2003).
All muscle relaxants do not share the same
mechanism of action or molecular structure.
What they have in common is a shared centrally
acting process that effectively depresses
postsynaptic reflexes, monosynaptic reflexes,
and gross motor activity. Soma is converted in
the body to meprobamate (Equanil), which is
considered a Schedule IV controlled substance
(Boothby, Doering, and Hatton, 2003). Equanil
is a carbonate derivative with tranquilizer
properties that has largely been replaced by
benzodiazepines. It is highly addictive. Soma is
considered a Schedule IV controlled substance
in some states but not at the federal level. Soma
is frequently obtained over the Internet from
pharmacies in Mexico and is often coingested
with other drugs such as alcohol and codeine.
Abusers of Soma and Vicodin state that the
effects of this drug combination are similar to
Heroin (Boothby, Doering, and Hatton, 2003).
Flexeril is similar in structure to amitriptyline
but does not cause the same effects as TCAs
such as widened QRS and ventricular
arrhythmias (Bebarta et al., 2011). Flexeril has
793
antihistamine, anticholinergic, and sedative
properties and accounts for 30% of all muscle
relaxant overdoses (Bebarta et al., 2011). There
have been case reports of the use of Flexeril
with SSRIs precipitatating serotonin syndrome.
Flexeril is a weak inhibitor of presynaptic
norepinephrine and serotonin, and any
substance with proserotonergic properties can
precipitate
this
syndrome
(Day
and
Jeanmonod, 2008). Toxic doses with
anticholinergic symptoms occur at doses of
more than 100 mg and can cause significant
rhabdomyolysis (Chabria, 2006).
Baclofen is an agonist at the GABA (B) receptor.
Symptoms of overdose can produce CNS
depression
and
respiratory
depression.
Seizure-like activity and paradoxical muscle
hypertonicity
have
been
reported.
Hallucinations, seizures, and hyperthermia
have been reported with withdrawal from
baclofen. The toxic dose of SMR varies
depending on drug tolerance and dependency.
Overdose can also depend on coingestion of
other drugs such as sedatives and alcohol.
Symptoms of overdose
Symptoms vary depending on the SMR used.
All typically cause altered mental status and
result in CNS depression. Most cause muscle
hyperreflexia. Hypotension can also occur.
Flexeril can cause anticholinergic signs and
symptoms. Soma can cause muscle rigidity and
794
hyperreflexia. Baclofen has caused coma,
respiratory depression, bradycardia, and
seizure-like activity.
Diagnostic testing and monitoring
Drugs can be detected on comprehensive
toxicology urine screening. CBC, extended
metabolic panel, CPK levels, standard drug
toxicology tests, ethanol, ASA, and Tylenol
levels should be completed. ECG monitoring
and monitoring of the airway and ventilation
status should be done. Intubation and
ventilation may be needed.
Antidotes/binding agents/treatments
There is no specific antidote or binding agent.
Activated charcoal can be given within 1 h of
ingestion. Because of extensive tissue
distribution of these drugs, dialysis and
hemoperfusion are not effective. Treatment is
supportive with maintenance of airway and
support of blood pressure with crystalloids.
Inotropic support may be needed. Hypotension
usually responds to IV crystalloids but use of
vasopressors such has norepinephrine may be
needed. Dopamine is very effective and has an
inotropic effect on the incidence of bradycardia
and hypotension due to its chronotropic effects
on the heart.
795
Clinical Pearls
Be aware that there are also implanted
intrathecal pumps that contain baclofen
which can malfunction or catheters can
migrate from their postoperative position
and cause inadequate or overinfusion of the
drug with concurrent signs and symptoms of
toxicity.
Psychiatric drugs
Drug overview
Drugs such as SSRIs, SSIs, monoamine oxidase
inhibitors
(MAOI/MAO),
lithium,
and
neuroleptics may be used as agents of overdose.
Most psychiatric drugs produce signs and
symptoms that can affect the neurological
system. Serotonin syndrome is caused from
excessive 5-hydroxytryptamine stimulation. It
can be caused by overdose, overuse, or
interactions between certain drug groups.
MAOIs used in combination with drugs such as
meperidine, DMX, SSRIs, and ecstacy can
predispose patients to the development of
severe serotonin syndrome (Boyer and
Shannon, 2005). Symptoms include altered
mental status such as coma, delirium, and
agitation. Autonomic dysfunction is common
and can include hyperthermia, flushing,
796
diaphoresis, tachycardia, and mydriasis.
Patients may also exhibit muscular rigidity,
tremors, and seizures. The diagnosis of
serotonin syndrome or toxicity can be very
confusing and generally accepted criteria from
toxicologists include Sternbach’s serotonin
toxicity criteria or Hunter’s criteria. Hunter’s
has been shown to be more sensitive and
specific than Sternbach’s criteria (Dunkley et
al., 2003). Hunter’s decision rules for
diagnosing serotonin toxicity involve the use of
well-defined diagnostic criteria. The single most
important is clonus, either spontaneously
inducible or ocular. Other signs and symptoms
include
agitation,
diaphoresis,
tremor,
hyperreflexia, hypertonia, and fever (Dunkley et
al., 2003) (see Table 13.2).
Table 13.2
syndromes.
Drug-induced
hyperthermia
Adapted from Dunkley et al. (2003); McAllen
(2010), Musselman and Saely (2013); and
Sternbach (1991).
Cause
Neuroleptic
malignant
syndrome
Serotonin
syndrome
Sympathom
syndrome
Use of
neuroleptic drugs
that block
dopamine
Use of
serotonergic
drugs/agonist
drugs
Drugs that al
of norepineph
dopamine, an
by enhancing
inhibiting
797
Drugs
Neuroleptic
malignant
syndrome
Serotonin
syndrome
Sympathom
syndrome
Exposure to
antipsychotic
drugs
Exposure to
SSRIs, MAOs,
SNRIs, and TCAs.
Other common
drugs: tramadol,
linezolid, fentanyl,
lithium,
dextromethorphan
Exposure to
amphetamine
methampheta
cocaine, ecsta
MAOs
Other drugs:
prochlorperazine,
metoclopramide,
and
promethazine
St John’s wart
Bath salts
(synthetic
canthinone
derivatives),
ecstasy, and
ondansetron
798
Neuroleptic
malignant
syndrome
General
Altered mental
symptoms status,
hyperthermia,
elevated CPK,
elevated
transaminases,
hypertension,
tachycardia,
cardiac
dysrhythmias,
incontinence,
abnormal
involuntary
movements,
leukocytosis
Serotonin
syndrome
Sympathom
syndrome
Altered mental
status,
hyperthermia,
elevated CPK,
elevated
transaminases,
hypertension,
tachycardia,
cardiac
dysrhythmias,
incontinence,
abnormal
involuntary
movements,
leukocytosis
Hyperthermi
psychomotor
agitation, alte
mental status
hallucination
electrolyte
disturbances,
CPK, seizures
rhabdomyoly
hypoxia, myo
infarction, an
arrhythmias
Rhabdomyolysis mydriasis,
Low serum iron nystagmus,
levels
shivering, and
rhabdomyolysis
Severe form:
metabolic
acidosis, coma,
multisystem organ
failure,
disseminated
intravascular
799
Severe forms
epilepticus, c
death
Neuroleptic
malignant
syndrome
Serotonin
syndrome
Sympathom
syndrome
coagulation, and
cardiac arrest
Muscular Muscular rigidity
symptoms is an early
symptom
(described as
lead-pipe
rigidity)
Tremor,
Psychomotor
hyperreflexia, and excitability
hypertonia are
symptoms; usually
more pronounced
in lower
extremities versus
upper
Rigidity is a
terminal event
Onset
Slow onset and
Rapid onset and
progression (24 h progression with
to days)
overdose or
addition of agonist
agents ( minutes
to within 24 h)
Clonus
No clonus
Varying onse
progression
depending on
and agents
Spontaneous or
No clonus
inducible
myoclonus/ocular
clonus/ankle
clonus
800
Neuroleptic
malignant
syndrome
Treatment Discontinue
neuroleptics
Supportive care:
core temperature
monitoring
external cooling,
IV fluids,
antipyretics,
benzodiazepines
Serotonin
syndrome
Sympathom
syndrome
Discontinue
Discontinue o
serotonergic agent agent
Supportive care:
core temperature
monitoring
external cooling,
IV fluids,
antipyretics are
usually not
effective,
benzodiazepines
Supportive ca
aggressive co
internal or ex
devices
Core tempera
monitoring ,
antipyretics,
benzodiazepi
In extreme cases,
non-depolarizing
paralytic agents
and mechanical
ventilation may be
needed
801
In extreme ca
non-depolari
paralytic agen
or barbiturate
mechanical
ventilation m
needed
Neuroleptic
malignant
syndrome
Serotonin
syndrome
Sympathom
syndrome
Blood work: CBC,
electrolytes, CPK,
iron levels,
cardiac
monitoring
Blood work: CBC,
electrolytes, CPK,
ABGs, cardiac
monitoring
Blood work: C
electrolytes, C
troponin I lev
ABGs, cardia
monitoring
Bromocriptine,
dantrolene, and
amantadine have
been used for
treatment in
severe cases
Cyproheptadine
hydrochloride , an
antihistamine that
blocks 5-HT, can
be administered
for severe cases
Dantrolene h
used in ecstas
overdose. Avo
B-blocking dr
cocaine overd
Bromocriptine
and dantrolene
should not be used
The difference between serotonin syndrome
and neuroleptic malignant syndrome (NMS)
can usually be made by physical examination
and use of Hunter’s criteria. NMS is a
hypodopaminergic state where bradykinesis
results in immobilization, stupor, akinesia,
“lead pipe rigidity,” fever, and autonomic
instability. It is unlikely to be dose-related, and
is rare in occurrences of overdoses (Gillman,
2011). Serotonin syndrome, on the other hand,
802
may be related to dosage or multiple SSIs/
SSRIs that have been overdosed or prescribed.
The excessive CNS serotonergic activity is
caused by increased 5-HT production from
tryptophan, increased reuptake inhibition from
SSRIs and cyclic antidepressants, increased
presynaptic release from sympathomimetics,
receptor agonism by tryptans, lithium, L-dopa,
and bromocryptine, and inhibited metabolism
by MAOIs (Brush, 2005).
Selective serotonin reuptake inhibitors
Drug overview
This category includes drugs whose mechanism
of action is to inhibit the reuptake of 5-HT
resulting in variable effects on other
neurotransmitters. Newer SSRIs are able to
inhibit the reuptake of both norepinephrine and
serotonin.
Symptoms
Patients usually present with symptoms 6–24 h
after a medication change or addition. Common
medications that are given for various medical
disorders such as Flexeril, fentanyl, Ultram,
Zofran, Reglan, Tegretol, Zyvox, and Demerol
have also been indicated in serotonin syndrome
(Ables and Nagubilli, 2010). SSRIs are safer
and better tolerated than MAO and cyclic
antidepressants. The basic action is to modulate
the reuptake of the neurotransmitter serotonin.
803
Common drugs that are classified as SSRIs are
Celexa, Lexapro, Prozac, Trazodone, and
Venlafaxine. The risk of developing serotonin
syndrome occurs when these drugs are used in
combination with each other or with other
MAOIs such as Nardil, isocarboxazid, and
Furoxone. St John’s wart, a popular herbal, also
partially acts as an MAOI.
Diagnostic testing and monitoring
Admission to a critical care unit is necessary.
General laboratory values should include CBC
and extended metabolic panel. Cardiac
monitoring and daily 12-lead ECG testing is
recommended until resolution of symptoms
occurs. If CNS depression or fever is present, a
chest X-ray and CPK level should be done with
particular attention to symptoms of serotonin
syndrome. Patients should be examined for the
presence of clonus. Drug levels are not readily
available and are not useful in the management
of overdose. Frequent monitoring of the QT and
QTc interval should be done. Patients may have
autonomic instability and if hypertension is
present, it is best managed with a short-acting
IV infusion of Esmolol (Eyer and Ziker, 2007).
Antidotes/binding agents/treatments
Withdrawal of the offending medication is
necessary. Activated charcoal can be given if
overdose is within the first couple of hours of
ingestion. Treatment is supportive using
804
advanced life support measures if needed.
Benzodiazepines should be given to manage
seizures. Hypotension should be managed with
IV crystalloid infusion; if the patient does not
respond to adequate volume resuscitation,
vasopressors may be needed. If shock states
persist, intra-aortic balloon pumping may be
needed to support cardiac function. Use of
paralytic agents may be needed to manage
muscular rigidity and tremors. External or
internal cooling devices may be needed to
manage fever. If any sustained-release
preparations were ingested, whole-bowel
irrigation should be employed. Cyproheptadine
has been used as an antidote in case reports.
Cyproheptadine is an antihistamine with both
anticholinergic and antiserotonergic properties,
and has mitigated symptoms in moderate to
severe forms of serotonin syndrome. Dosage
recommendations are 12 mg initially followed
by an additional 2 mg every 2 h for persistant
symptoms. A maintainence dose of 8 mg every
6 h can be administered if needed. Urinary
retention is a common side effect (Ables and
Nagubilli, 2010). Chlorpromazine has also been
used and the starting dose is 50–100 mg IM
(Eyer and Ziker, 2007).
805
Clinical Pearls
Citalopram and escitalopram can cause wide
complex tachycardias. All SSRIs have various
half-lives, the most common being one day.
The SSRI Fluoxetine has a half-life of up to 4
days. Some of the SSRIs affect cytochrome
(CYP450), and coingestion of other drugs
that affect this enzyme should be considered.
There have been many case reports of
interactions with citalopram (Celexa) and
fluconazole. Fluconazole inhibits CYP2C19
and citalopram is a substrate of 2C19.
Inhibition of its metabolism can precipitate
serotonin toxicity (Levin et al., 2008).
Monoamine oxidase inhibitors
Drug overview
This drug class is used to treat severe
depression. Serious toxicity can occur with this
class of drugs either from overdose or
interactions between the drug and certain food
groups. MAOIs are intracellular enzymes that
break down and inactivate monoamine.
Monoamine is responsible for the interruption
of catecholamines within the neurons in the
brain. MAOIs are also found in the liver and
intestinal system, where they metabolize
tyramine and prevent its entry into the systemic
806
circulation. Serious toxicity results from the
excessive release of neuronal stores of
vasoactive amines, the inhibition of metabolism
of catecholamines, interaction with certain
drugs, or release and absorption of large
amounts of dietary tyramine, which causes
release of catecholamines from neurons. There
are multiple interactions between MAO/MAOIs
and other drug classes. Significant interactions
exist between many SSRIs, tramadol, demeral,
DMX, and amphetamines. Food interactions
exist with beer, red wine, chesses, fava beans,
yeasts, smoked, pickled, or aged meats, snails,
and chicken liver (see Tables 13.3 and 13.4).
Table 13.3 MAO/MAOI drug interactions.
Adapted from Olson (2012) and Wimbiscus et al.
(2010).
Amphetamines
Buspirone
Cocaine
Fluvoxamine,
fluoxetine
LDS
Imipramine
Methyldopa
Paroxetine
Phenylephrine Sertrali
Tryptophan
Dextrom
Meperi
Amitryptyline methad
Reserpine and
Tyramine-containing related
compounds
foods and drugs
Terbutaline
(no longer
available in
the United
States)
Norepin
Albuterol
Dopamine
Ketamine
Isoprot
Hydroc
Methylphenidate
Pseudoephedrine Salmeterol
807
Phente
Table 13.4 MAO/MAOI food interactions.
Adapted from Olson (2012) and Wimbiscus et al.
(2010).
Red
wine
Aged cheeses
Sauerkraut Soybean
curd
Tap
beers
Aged meats
Snails
Cured meats
Dry
Spoiled or
Pickled
sausages bacteria-contaminated herring
meats
Concentrated Bro
yeast
bea
pod
Chicken liver Fav
bea
Symptoms of overdose
Symptoms are usually delayed for up to 12 h
and symptoms and death can occur days after
overdose. Most symptoms of acute intoxication
are neurological manifestations related to CNS
hyperactivity. These develop from excessive
concentrations of catecholamines at the nerve
terminals. Patients may experience headache,
agitation,
hypertention,
tachypnea,
hyperthermia, nystagmus seizures, muscular
rigidity, myoclonus, coma, and mydriasis. As
poisioning becomes severe, hypotension,
bradycardia, and asystole can occur, resulting
from depletion of cathecholamines at nerve
terminals. Late effects of toxicity may include
rhabdomyolosis, disseminated intravascular
coagulation,
pulmonary
edema,
and
myoglobinuric renal failure.
808
Soy
sau
Diagnostic testing and monitoring
ECG monitoring for a minimum of 24 h in
critical care is needed. CBC and complete
metabolic panel along with serial 12-lead ECGs,
ABGs, and CPK levels are recommended.
Antidotes
Activated charcoal is given if ingestion has
occurred within 1–2 h. Initiate other supportive
care such as maintenance of the airway,
treatment with benzodiazepines for seizures,
and crystalloid IV fluid administration for
hypotension. Severe hypertension is initially
treated with a short-acting titratable drug such
as nitroprusside. Because hypertension can be
quickly followed by hypotension, longer agents
should not be used. Beta blockers should be
avoided because they may cause unopposed
alpha stimulation and elevated blood pressure.
If patients develop reflex bradycardia, avoid the
use of atropine as it can also cause dangerously
high hypertension. Hemodialysis is not effective
in MAO/MAOI toxicity because these are highly
protein-bound medications.
Clinical Pearls
Amphetamines may show up as positive on a
drug screen for tranylcypromine and
selegiline because they are structurally
809
similar and metabolized into amphetamines
and methampetamines.
Lithium
Drug overview
Lithium is a drug used in psychiatric medicine
to treat bipolar and unipolar depression.
Therapeutic serum concentrations are 0.8–1.25
mEq/l. It is available in both immediate and
sustained-release forms.
Lithium competes with NA + for ion transport.
It enhances serotonin and acetylcholine effects
and acts as an inhibitory second messenger via
inositol phosphates. With toxic levels it
suppresses neural excitation and synaptic
transmission. Toxicity depends on chronic or
acute ingestion. Chronic toxicity is usually from
decreased renal clearance and acute toxicity
occurs with deliberate or accidental overdose.
Absorption occurs within 1–6 h for immediate
release and is prolonged for up to 48 h in
sustained-release forms. The half-life is usually
24 h but can be prolonged for up to 48 h. Acute
ingestion of 20–30, 300 mg tablets would likely
cause serious toxicity. Ninety-five percent of
lithium is cleared by the kidney. Renal tubular
reabsorption is increased in sodium-depleted
and dehydrated states.
810
Symptom of overdose
Most symptoms of acute intoxication consist of
neurological manifestations and GI symptoms.
Mild toxicity (levels <1.5 mEq/l) usually
presents with nausea, vomiting, lethargy, fine
tremors, and memory impairment. Moderate
toxicity (levels of 1.5–3.0 mEq/l) usually
presents
with
confusion,
agitation,
hyperreflexia,
hypertension,
tachycardia,
ataxia, nystagmus, extrapyramidal symptoms,
and dysarthria. Severe toxicity (levels >3.0
mEq/l) results in bradycardia, seizure, coma,
hypotension, and hyperthermia. Lithium levels
do not always correlate with clinical toxicity
because of their slow distribution. After initial
early ingestion, an elevated level that would
correlate with toxicity but no symptoms may be
seen because of measurement before final
tissue distribution. Nonspecific ECG changes
can also occur including U waves, flat, biphasic,
or inverted T waves, and sinus, junctional, or
atrioventricular
(AV)
nodal
blocks.
Leukocytosis may also develop. Nephrogenic
diabetes
insipidus
with
dilute
urine,
hypernatremia, and elevated blood urea
nitrogen (BUN) and creatinine is also common.
Diagnostic testing and monitoring
Lithium levels should be measured every 2–4 h
until peak levels are seen. Monitoring of CBC
and complete metabolic panel should be done
daily until levels are trending down. Continuous
811
ECG monitoring is needed until lithium levels
have normalized.
Antidotes/binding agents/treatments
There is no specific drug antidote. Treatment
depends on symptoms and lithium blood levels.
Activated charcoal can be given within the first
1–2 h of acute ingestion but is ineffective in
chronic toxicity. Whole-bowel irrigation should
be used for sustained-release toxicity. Maintain
a patent airway in patients who are obtunded. If
dehydration is present, crystalloid fluids are
administered with 1–2 l of normal saline
followed by 0.45% normal saline. Monitor
serum metabolic panel to manage fluid balance.
Loop diuretics or mannitol are not
recommended as initially they may increase
lithium excretion but if the patient becomes
water- or salt-depleted, lithium reabsorption
will increase and toxicity will worsen. Lithium
is a small ion, is not protein-bound, and has a
small apparent volume of distribution and is
able to be removed by dialysis. Dialysis is
indicated for a patient with severe neurological
symptoms and two consecutive lithium levels
greater than 4.0 mEq/l. There should be no
history of previous acute lithium toxicity.
Dialysis can also be considered in patients who
would not be able to handle adequate fluid
replacement such as patients with heart failure,
edematous states, and pulmonary edema.
Lithium levels should be redrawn 6 h after
812
dialysis as lithium is only removed from the
plasma during dialysis. Once lithium from the
intracellular space equilibrates with the serum,
a higher level may occur. If the level is high or
severe and symptoms persist, the patient
should have dialysis repeated.
Clinical Pearls
Benzodiazepines should be given for seizures.
Volume replacement should target a goal of
1–3 ml/kg of urine output per hour. If
hyperthermia is present, cooling measures
should be started. Although charcoal is
usually ineffective, many lithium overdoses
contain coingestion so it should be
considered. Dialysis may also be effective in
acute or chronic intoxication but generally is
not useful in chronic toxicity.
Neuroleptics
Drug overview
Neuroleptics are drugs that are used for
treatment of a variety of psychological
disorders. Psychotic disorders are thought to
occur from an excess of dopamine in certain
areas of the brain. Nondopamine receptors are
also thought to be involved. These drugs are
used to treat agitation, hallucinations, and
acute delirium. Drugs in this class are agents
813
that contain antipsychotic properties and
extrapyramidal symptoms (EPS). EPS are
thought to arise secondary to excess dopamine
blockade, which leads to tremor, rigidity, and
other parkinsonian effects. Effects can also
occur in the endocrine system and can cause
sexual dysfunction. These drugs can also cause
akathisia, which is an inner feeling of the need
to be in constant motion. Patients are
compelled to constantly move or rock
themselves. The cause of NMS is thought to be
secondary to dopamine deficiency. Excess
serotonin has been shown to cause dopamine
deficiency. Usually NMS presents over the
course of several days and always presents with
fever.
Neuroleptic agents are dopamine receptor
antagonists. They may block four different
pathways for dopamine. Symptoms of overdose
will depend on which drug is used and which
pathway it has blocked. The primary
mechanism of action of these drugs is
postsynaptic blockade of the D-2 receptor but
some also have H1 receptor blockade,
peripheral alpha receptor blockade, or
muscarinic receptor blockade. Neuroleptics
may be classified as older typical agents. These
usually carry more of a risk of EPS and seizures
(Hedges, Jeppson, and Whitehead, 2003).
Newer atypical agents generally have fewer
EPS. Low-potency medications can cause more
sedation, anti-acetylcholine (ACH), and
814
orthostatic
hypotension.
High-potency
medications can cause more EPS.
Symptoms of overdose
Side effects of toxicity may include hypotension,
prolonged QT interval, tachycardia, and dry
mucous membrane. Depending on the drug
ingested, symptoms are varied but most include
the CNS and cardiovascular system. Dystonic
reactions, parkinsonism symptoms, seizures,
hypotension, cardiac arrhythmias, hypo- or
hyperthermia, and decreased GI motility can
occur. Symptoms of anticholinergic toxidrome
for some drugs may be seen.
Diagnostic testing and monitoring
Patients should be admitted to a critical care
unit. Continuous ECG monitoring and airway
protection may be needed depending on altered
mental status symptoms. Drug levels are
generally not available. CBC, ABGs, and
complete metabolic profile should be obtained,
and drug toxicity panels should be ordered to
rule out coingestions.
Antidotes/binding agents/treatments
Recognition of NMS is important so treatment
is not delayed. Care is supportive and there is
no specific antidote. Because neuroleptics tend
to lower the seizure threshold, seizures may be
common and respond well to benzodiazapams.
815
Hypotension is best treated with IV crystalloids
and pure alpha agonists such as norepinephrine
and phenylephrine. Use of mixed beta and
alpha adrenergic agents such as epinephrine
and dopamine should be avoided as they can
worsen hypotension through vasodilation from
unopposed beta stimulation. Hemodialysis is
not effective due to the large volume of
distribution and high protein binding.
Dantrolene and bromocriptine have also been
used to relax skeletal muscles and treat
parkinsonism
symptoms
from
abrupt
discontinuation
of
dopamine-stimulating
medications but their use remains controversial
(McAllen and Schwartz, 2010).
Clinical Pearls
Common dystonic reactions include
oculogyric crisis, which is an upward-gaze
paraylysis, torticulosis, retrocollis, scoliosis,
and abdominal wall spasms. Dystonic
reactions usually occur within 4–60 days but
can occur immediately after dosing of the
offending drug. Treatment of dystonic
reactions or EPS is fairly simple. Treatment
consists of the use of benzodiazapines and
anticholinergic drugs. Doses for Benadryl
should be 50–100 mg or 1–2 mg/kg. Ativan
1–2 mg IVP and Cogentin 1–2 mg IM or 1–4
mg/po may be used. Avoid all class 1A
816
antiarrhythmics as these can prolong the QT
interval and exacerbate arrhythmias.
Tricyclic antidepressants
Drug overview
Cyclic antidepressants are drugs used to treat
depression. Poison Control Centers in the
United States report TCAs as the third most
reported type of poisoning. The most common
TCAs reported in overdose are amitriptyline,
dosulepin, and imipramine (Howell and
Chauhan, 2010). TCAs work by inhibiting the
reuptake of the transmitter’s serotonin,
norepinephrine, and dopamine, resulting in
greater availability of these transmitters at the
synapse. They generally have a low therapeutic
index and serious overdose can happen with
less than 10 times the therapeutic dose. TCAs
also have secondary effects. They inhibit fast
sodium channels in the myocardium, which can
cause widened QRS and inhibit calcium entry
into the myocardial cells, decreasing cardiac
contractility. They also inhibit cholinergic
responses and produce classic anticholinergic
toxicity. Inhibition of the alpha-adrenergic
receptors may occur, causing peripheral
vasodilation.
Common drugs include amitriptyline, doxepin,
imipramine, and Flexeril. Tricyclic toxicity
817
generally affects the cardiac system and CNS.
Anticholinergic effects of these drugs delay
gastric emptying so that absorption is slow and
erratic. Onset of action may be as quick as 30
min. Peak concentrations occur within 2–6 h
after ingestion. Many have active metabolites.
They are extensively bound to plasma proteins
and body tissues, resulting in large volumes of
distribution and long half-lives. Elimination is
variable and may be between 8 and 30 h. Some
are available in sustained-release form and can
have
significant
delayed
peak
serum
concentrations. The general toxic dose is 10–20
mg/kg. They are metabolized by the liver.
Symptoms of overdose
Symptoms include anticholinergic effects,
cardiac arrhythmias, and QRS prolongation
greater than 0.10–0.12 s, hypotension
secondary to venous dilation and myocardial
depression, and seizures that may be persistent
and lead to status epilepticus. QRS
prolongation is the single most important
indicator of toxicity. Patients can deteriorate
rapidly. Most toxic responses to tricyclic
overdose occur within the first 6 h.
Diagnostic testing and monitoring
Overdose should be suspected in any patient
presenting with lethargy, coma, seizures, and
QRS prolongation greater than 0.12 s in the
limb leads. Patients should be monitored in a
818
critical care unit. Serial 12-lead ECGs should be
done on admission and hourly for the first 6 h.
Standard drug screens should be used to rule
out coingestions. Decontamination with
activated charcoal should be done with
ingestions that have occurred within 1 h. CBC,
comprehensive metabolic panel, ABGs, and
CPK levels should be drawn. Patients who are
given bicarbonate or placed on a bicarbonate
drip need serial ABGs monitored. Death from
toxicity usually occurs within a few hours of
overdose and results from ventricular
fibrillation, intractable cardiac arrhythmias,
cardiogenic shock, seizures, and hyperthermia.
Development of bradyarrhythmias is a very
ominous finding. Monitoring the QRS interval
is a much more reliable measure of toxicity than
TCA laboratory assays.
Antidotes/binding agents/treatments
Charcoal can be administered within the first
hour of ingestion. If QRS prolongation is
present, sodium bicarbonate should be
administered. The mechanism of action is
thought to be a combination of sodium load
along with serum alkalization, which negates
the fast sodium channel inhibition in the
myocardium. Alkalization of the serum can also
cause increases in plasma protein binding of the
drug. Sodium bicarbonate dose is usually 1–2
mEq IVP until the QRS narrows to normal
limits or serum pH is 7.50–7.55. An IV infusion
819
can then be given of 3 amps of sodium
bicarbonate in 1 liter of D5W administered at
75–150 cc/h for 6 h. Use of antiarrhythmic
drugs class IA and IC, which block sodium
channels, is contraindicated. Class III
antiarrhythmics such as amiodarone and
bretylium are also contraindicated. Lidocaine, a
class IB, can be used safely in refractory
arrhythmias. Physostigmine is not helpful to
manage anticholinergic symptoms and has been
shown to precipitate seizures and can also cause
asystole (Kerr, McGuffie, and Wilkie, 2001).
Seizures
should
be
treated
with
benzodiazepines and if intractable seizures are
present, the use of phenobarbital is useful.
Phenytoin can also be used as it is a class IB
antiarrhythmic. Intubation and ventilation may
be needed with altered mental states or
cardiogenic shock states. Hypotension should
be treated with IV crystalloid infusions of
normal saline with the use of inotropic drugs
such as dopamine or norepinephrine if needed.
Clinical Pearls
There are new therapies being developed in
antibody fragment (Fab) therapies for TCA
overdose. Fab therapies have a high binding
capacity for the toxin and work like Digibind
in digoxin overdose. The procedure for
antibody isolation is very complex and
820
expensive to develop and so far has required
large amounts of Fab. There have been cases
of small human studies with mild TCA
overdose that have shown success using this
therapy but it is not yet approved for use in
the United States and studies are continuing
(Howell and Chauhan, 2010). There have
also been several case reports that have used
ILE therapy in TCA overdose that is
unresponsive to standard toxicology
treatment (Roberts, 2010).
Carbon monoxide
Drug overview
Poisoning from carbon monoxide (CO) is a
common problem accounting for approximately
50 000 emergency department visits each year
in the United States, more commonly seen in
the fall and winter (Ruth-Sahd, Zulkosky, and
Fetter, 2011). Causes of CO poisoning include
exposure or use of improperly ventilated fuels
or impaired furnace functions, industrial
chemicals such as paint stripper, or exhaust
fumes. CO is a colorless, odorless gas that
exerts a pathological effect on the body through
a variety of mechanisms and causes
approximately 2700 deaths annually according
to the Centers for Disease Control. Mortality of
patients treated in a hospital setting is 3% and
821
significant mortality correlates with fire as a
source of CO2, loss of consciousness,
carboxyhemoglobin level, arterial pH, and
presence of endotracheal intubation during
hyperbaric treatment (Hampson and Hauff,
2008).
Pharmacology
CO poisoning leads to impairment in oxygen
delivery and utilization of oxygen by the body.
Impairment of oxygen delivery causes an
oxidant stress injury. High-affinity CO binds to
hemoglobin, resulting in high levels of
carboxyhemoglobin. This causes decreased
oxygen-carrying capacity from the displacement
of hemoglobin and causes a shift to the left on
the oxyhemoglobin dissociation curve. CO
increases levels of cystosolic heme, which leads
to oxidative stress. The binding of platelet heme
protein and cytochrome c oxidase interrupts
cellular respiration, which induces a stress
response and activates hypoxic inducible factor.
Acute inflammation occurs through a variety of
mechanisms and pathways and results in both
neurological and cardiac injury (Weaver, 2009).
Organs with high metabolic demands such as
the heart and brain are the most affected by CO
toxicity.
Symptoms
Symptoms of acute poisoning are vague and
nonspecific. They can include muscle aches and
822
tenderness, fatigue, headaches, and dizziness,
similar to viral infection symptoms. Severe
exposure to CO can result in loss of
consciousness,
seizures,
cardiac
arrest,
pulmonary edema, myocardial infarction from
angina, and death. Symptoms of chronic
poisoning may differ from acute poisoning and
may include memory deficits, fatigue,
polycythemia, neuropathy, and difficulty with
concentration. Levels greater than 3% in
nonsmokers and greater than 10% in smokers
are considered positive for exposure. The level
generally does not correlate with symptoms or
duration of exposure (Weaver, 2009). Later
adverse outcomes may not be related to actual
levels but more to inflammatory effects at the
cellular level. Long-term effects can include
motor and gait disturbances, hearing and
vestibular abnormalities, and peripheral
neuropathies. Patients can also develop
CO-induced
delayed
neuropsychiatric
syndrome, which develops after injury and
apparent recovery and includes declining
cognitive functioning, dementia, development
of parkinsonism, and personality changes. Most
of these symptoms may resolve within a year
after recovery.
Diagnostic testing and monitoring
Monitoring should include neurological testing,
CBC, extended chemistries, serial ABGs, and
serum carboxyhemoglobin (CO-Hgb) testing.
823
The use of a co-oximeter is preferred to routine
blood gas analyzers, which only measure
oxyhemoglobin. A co-oximeter measures
different levels of normal and abnormal
hemoglobins as opposed to calculated values of
carboxyhemoglobin. In cases of severe CO
poisoning, lactic acidosis and anion gap
metabolic acidosis may be present. Pulse
oximetry is frequently inaccurate and may be
falsely elevated in cases of significant
poisoning. If severe coma from poisoning is
present, head CT scanning may be necessary to
identify severe hypoxia or ischemic cellular
damage. Bilateral globus pallidus low-density
lesions have been reported in severe posionings
and may not be present until several days after
exposure. Patients may also have symmetric
white matter lesions on magnitic resonance
imaging (MRI) (Kao and Nanagas, 2004). ECG
and cardiac isoenzymes should also be
performed to assess for any ischemic changes in
cardiac rhythm. Patients with a history of
myocardial disease are more susceptible to
myocardial injury.
Antidotes/binding agents/treatments
Supportive care, high-flow supplemental
oxygen for treatment of hypoxia, and
accelerated removal of CO are urgent
treatments. Use of a 100% non-rebreather
oxygen mask or intubation with 100% oxygen
until carboxyhemoglobin levels are less than 5%
824
is recommended (Weaver, 2009). Abnormal
vital signs should be treated aggressively. In
cases of cardiac instability, standard therapy
with antiarrhythmics, ASA, and nitrates is
effective. In cases of severe poisoning with
neurological deficits, seizures, and cardiac
dysrhythmias, the use of a hyperbaric oxygen
chamber may be needed and has been shown to
reduce adverse neurological outcomes (Kao and
Nanagas, 2004). The use of hyperbaric oxygen
remains controversial (Weaver, 2009).
Clinical Pearls
In cases of deliberate CO poisoning,
coingestions of other substances must be
ruled out. Long-term chronic exposure to CO
can causes symptoms of chronic fatigue,
memory deficits, neuropathy, polycythemia,
recurrent infections, and vertigo. Symptoms
such as headache, neurological problems,
and memory deficits may persist after
treatment for up to 6 weeks and beyond
(Weaver, 2009).
Hydrocarbons and toxic inhalants
Drug overview
These are substances that usually have
mind-altering effects when inhaled. They are
used by individuals to “get high.” The practice
825
of using inhalents is referred to as huffing,
sniffing, or bagging. Huffing is the wetting of
cloths and directly breathing in and out,
sniffing is direct use out of the container, and
bagging is discharging the toxin into a bag and
inhaling. Inhalation provides effects of
euphoria (Simlai and Khess, 2008). Some
common toxic inhalants used are white out,
toluene (methylbenzene) paint stripper, glue,
benzene, Freon (fluorocarbons), nitrates (for
sexual vasodilator effects), and felt tip marking
pens. Individuals who experiment with toxic
inhalents are usually adolestants, professional
adults who have access to inhalants, and
homosexual groups. National Poison Data
System (NPDS) collects data in real time from
60 US Poison Control Centers. The prevalence
of inhalant use decreased by 33% from 1993 to
2008 and the highest use was observed in the
12–17-year-old age group, with peak ages of
14–15 years. Males comprised 73.5% of cases
where gender was known. The highest
prevalence was seen in western mountain states
and West Virginia. Common toxins include
gasoline, propellants, and paint. Butane,
propane, and air fresheners had the highest
fatalities (Marsolek, White, and Litovitz, 2010).
Pharmacology
Volatile substance abuse can sensitize the
myocardium to endogenous cathecholamines
and predispose individuals to ventricular
826
arrhythmias and asystole. They are highly
lipid-soluble and take seconds to have an effect.
Bagging offers the highest concentration and
most effects. Pharmacology of inhalants will
vary by the substance inhaled. Most acute
effects last less than 2 h but permanent CNS
effects can be seen with chronic use. Generally,
acute high-level exposures to volatile
substances are usually reversible while chronic
exposures carry the risk of permanent disability
(Iqbal, 2001). Metabolic processes for toxic
effects vary and depend on the substances
inhaled and cellular damage and effect. Toluene
amounts as small as 15–20 ml have been
reported to cause significant toxicity.
Diagnostic testing and monitoring
Diagnosis is usually made by history of
inhalation, either deliberate or accidental.
Depending on organ system involvement, signs,
and symptoms, patients may need to be
monitored in a critical care unit. ECG
monitoring and oxygen saturation monitoring
should be conducted continuously. Standard
drug panels, CBC, electrolytes, CPK, ABG, and
LFTs should be drawn and monitored based on
symptoms of organ toxicity. A chest radiograph
should also be obtained to rule out pulmonary
toxicity due to aspiration or inhalation injury.
827
Signs and symptoms
Common symptoms involving toxic inhalant
use are euphoric actions, ataxia, slurred speech,
various altered mental status, GI effects such as
nausea and vomiting, and respiratory difficulty.
Organs that are particularly vulnerable to
inhalents are the kidneys, with distal tubular
acidosis often found. Respiratory symptoms
include acute respiratory distress syndrome and
aspiration. Hepatic system effects include liver
necrosis, and cardiovascular system effects can
include arrhythmias and cardiac arrest. Toxic
inhalant use can also cause rhabdomyolysis and
many hematological derangements. Toluene
use has been linked to leukoencephalopathy,
brain stem abnormalities, cranial neuropathies,
and
cerebellar
syndrome
(Filley
and
Kleinschmidt-DeMasters, 2001). Hexacarbons,
which are present in glue and solvents, can
cause toxic neuropathies that usually recover
slowly over many months (Morrison and
Chaudhry, 2012).
Antidotes/treatment
Care is supportive. In accidental inhalation, the
patient should be removed from exposure.
Remove all contaminated clothing items and
wash all exposed skin with soap and water.
Irrigate eyes with water or saline. If coma and
bronchospasm occur, protect airway and
administer
bronchodilators.
If
cardiac
arrhythmias occur, sympathomimetics drugs
828
such as epinephrine can worsen symptoms.
Beta blockers such as propanolol or esmolol are
recommended.
Clinical Pearls
Toluene, which is present in glue, paint, and
solvents, is a common agent of abuse, readily
available and cheap. It is a known neurotoxin
and in chronic users usually produces
extensive cerebellar dysfunction and gait
ataxia, which is usually permanent. It has
been postulated that a genetic link to
concentrations of P450 enzymes that are
present in the body and vulnerability to
permanent disabilities with use of inhalants
may be due to the bioactivation of the
metabolic processes involved to detoxify
inhalants (Iqbal, 2001).
Cardiac medications
Drug overview
Beta blockers, calcium channel blockers,
nitrates, and digoxin are cardiac medications
that may result in overdoses.
Beta blockers—examples include Coreg,
metropolol, and labetalol. These drugs are
generally prescribed for hypertension,
dysrhythmias, angina, vasovagal syndrome,
829
migraines, and panic disorders. They can
also be used for the treatment of
thyrotoxicosis. Beta blockers work by
blocking β-adrenergic receptors of the
peripheral nervous system. They inhibit
binding of epinephrine and norepinephrine
to G- protein β-adrenergic receptors in the
heart, kidney, and eyes, which are β1
receptors. They also inhibit β2 receptors
present in blood vessels, bronchioles, liver,
and pancreas. They may also bind to the β
receptors and activate phosphodiesterase,
which increases cyclic adenosine
monophosphate (cAMP). Beta blockers may
be cardioselective and may only block β1
receptors, may have sodium channel
blocking, or have membrane stabilizing
effects and antiarrhythmic effects. The
half-life of certain types of beta blockers can
be severely prolonged based on the patient’s
hepatic and renal clearance. Some beta
blockers may be more lipophilic, such as
propranolol, which crosses fatty cell
membranes and affects the blood–brain
barrier more readily. This can produce more
CNS symptoms in overdose such as seizures
and coma (see Table 13.5).
Beta blocker symptoms of overdose.
Generally, symptoms occur within 20 min to
1 h. Most effects are seen within 6 h except
with time-released formulas and Sotolol,
whose effects can be seen for days. These
830
effects include hypotension, hypoglycemia,
seizures, and bradycardia. There can be
various degrees of AV blocks and ventricular
arrhythmias that can lead to cardiac arrest.
Both CCBs and beta blockers typically cause
prolongation of the PR interval and QRS
prolongation.
Beta blocker diagnostic testing and
monitoring. There are no specific tests
available at the hospital for drug level
testing in beta blocker overdose. Generally,
toxic effects may be seen with two to three
times the therapeutic range. Admission to
critical care is needed. Tests should include
continuous ECG monitoring, serial 12-lead
ECG, BP monitoring, and complete
metabolic panel. Chest X-ray and serial
ABGs may be necessary. Protection of the
airway with intubation and ventilation may
be needed in situations involving
cardiogenic shock states. Beta 2 blockade
can also cause increased airway resistance,
especially in patients with lung disease.
Frequent monitoring of blood glucose levels
should be done due to hypoglycemia and
hyperglycemia secondary to impaired
glycogenolysis.
Beta blocker antidotes/binding
agents/treatment. Charcoal and gastric
lavage can be used if time of overdose is
known and may be effective within the first
hour. In sustained-release forms, repeated
831
doses may be necessary. Whole-bowel
irrigation and cathartics for
sustained-release forms may be used.
Aggressive fluid hydration is recommended
and airway protection may be needed if
signs and symptoms of profound cardiac
instability and shock occur. Be aware that
there are many combination cardiac
prescriptions so coingestion is common. For
mild symptoms of bradycardia and
hypotension, fluids and atropine may be all
that are needed.
Glucagon is the treatment of choice for
hypotension and bradycardia. Doses of 5–10
mg IV bolus are usually needed followed by
1–5 mg/h infusion. Calcium chloride IV can
be given at a dose of 1 g of 10% solution or
calcium gluconate 30 ml of a 10% solution
can be administered. Infusion of calcium
will increase inotropic effects of the heart.
Catecholamines may be effective, but large
doses may be needed. Drugs such as
norephinephrine, dopamine, dobutamine,
Isuprel, and epinephrine can all be effective.
Keep in mind that these drugs can be
proarrhythmic. Epinephrine may be used at
doses of 1–4 μg/min. Sodium bicarbonate
may be used for wide complex conduction
defects caused by membrane-depressant
effects at a dose of 1–2 mEq/kg. Heart rate
may be refractory to atropine but it is safe to
use. Aggressive fluid resuscitation is usually
832
needed. Cardiac ultrasound may be useful.
QT prolongation from Sotolol can be treated
with magnesium, isoproterenol infusion, or
pacemaker insertion and overdrive pacing.
Cardiovascular instability unresponsive to
standard therapy may need temporary
transvenous pacemaker or intra-aortic
balloon pumping therapy. Hypoglycemia is
frequently seen most often in children and
seizures should be treated with glucose.
Clinical Pearls—Beta Blocker
If intubation is needed, pretreatment with
atropine should be considered to mitigate
potential vagal-induced bradycardia
(Anderson, 2007). Coreg and labetolol are
known to cause significant hypotension
due to their combined beta 1 blockade and
vasodilating effects. Labatolol may also
cause hyperkalemia in patients with renal
failure due to the increase in insulin
secretion from beta-adrenergic agents,
which augments cellular potassium
uptake (Anderson, 2007). Newer
therapies involving IV calcium and
high-dose insulin–glucose therapy have
been used successfully.
Calcium channel blockers. CCBs are
drugs most commonly prescribed to treat
833
angina, atrial arrhythmias, and
hypertension. They decrease myocardial
oxygen demand and increase coronary blood
flow. In 2008, the American Association of
Poison Control Centers reported 10 398
exposures to CCBs resulting in 12 deaths
and 63 major adverse outcomes (Horowitz,
2012). Overdose of CCB can result in
arrhythmias and severe hypotension and
shock, leading to ventricular fibrillation,
asystole, and cardiac arrest. Patients who
are asymptomatic are unlikely to develop
symptoms if ingestion of immediate release
is greater than 6 h from presentation, 18 h
for modified release, and 24 h for sustained
release (Baud et al., 2007).
CCB pharmacology. CCBs inhibit the
movement of calcium ions into the cells by
interfering with the action of the
voltage-gated calcium channels. As calcium
enters into the cardiac myocytes, three
results occur: negative inotropic,
chronotropy, and dromotropy actions. These
actions cause impaired impulse and
conduction in the sinoatrial and AV nodes,
which slows heart rate and may cause AV
blocks.
CCB symptoms of overdose. Symptoms
of overdose include varying forms of AV
block and cardiovascular collapse, metabolic
acidosis, and shock states. Hypotension and
bradycardia are common. Patients with
834
severe poisoning may present with heart
rates less than 50 and systolic blood
pressure less than 100. Hyperglycemia
occurs from the inhibition of
calcium-dependent insulin release. Other
symptoms include nausea, vomiting, and
lethargy.
CCB diagnostic testing and
monitoring. Patients should be monitored
in a critical care unit with continuous ECG
monitoring for symptoms of hypotension,
bradycardia, and AV blocks. Serial 12-lead
ECGs should be performed. Clinical testing
of blood levels for CCB is generally not
available. Standard drug screens should be
utilized to assess for coingestions. If patients
are on digoxin or coumadin, digoxin levels
and PT/INR should also be done. CBC and
extended metabolic panel should be done.
Patients on continuous insulin and glucose
therapy should have Q1 hour fingerstick
glucose levels. Hyperglycemia can occur as
CCB inhibits release of insulin. For
refractory shock, hemodynamic monitoring
and ECG should be done (Baud et al., 2007).
CCB antidotes/binding agents/
treatment. Activated charcoal should be
given if ingestion is within 1 h. Whole-bowel
irrigation with Golytely 2 l/h should be used
for extended-release formulas. Boluses of 1 g
of calcium chloride every 15–20 min, for a
total of four doses, or 1 g every 2–3 min can
835
also be utilized if CCB toxicity is verified.
Monitoring of ionized calcium levels should
be utilized. Large doses up to 10 g may be
needed. Calcium has a variable effect on
hypotension but has a minimal effect on
bradycardia. Avoid giving calcium to a
patient with concomitant cardiac glycoside
toxicity (digoxin) as fatal arrhythmias can
develop. Initiate high insulin/glucose
therapy early for severe CCB overdose.
Administration of insulin 0.1–1 μ/kg/h with
concurrent dextrose infusion of D10W or
D25W may be warranted. Titration of both
should be done to maintain normal serum
glucose levels. This therapy has been shown
to stabilize cardiac output by affecting
myocardial function, catecholamine release,
modulation of the inflammatory cascade,
and cellular apotosis. If patients are
receiving this therapy, glucose monitoring
should be performed every 20–30 min.
Glucagon can be given at doses of 5–15 mg
over 1–2 min for hypotension. Dosages can
be repeated every 3–5 min. Response is
usually seen within 1–3 min with peak
effects at 5–7 min. Glucogen has a short
half-life so if resolution of symptoms occurs,
an infusion can be started at 2–10 mg/h in
adults. Glucagon’s therapeutic effects may
decline over time due to loss of ability to
increase cAMP levels and in some situations
repeated boluses may be preferred
(Anderson, 2007). Glucagon activates
836
adenylate cyclase, which is independent of
the B receptor. Atropine can be used for
CCB overdose but is usually ineffective. IV
crystalloids should be given for hypotension
but frequently inotropic medications are
needed. Dopamine works well for
bradycardia and hypotension.
Norepinephrine and vasopressin may be
needed for additional management of
hypotension. Milrinone or Inocor, both of
which are phosphodiesterase inhibitors,
may be useful to support cardiac
contractility. On initial infusion they can
cause hypotension. Patients with refractory
hypotension may need intra-aortic balloon
pumping therapy. Patients with refractory
bradycardia and high-grade AV blocks may
require ventricular pacemaker insertion.
Clinical Pearls—CCB
Severe cardiac toxicity usually doesn’t
respond to single-dose therapy and
usually requires multiple-drug
combination modalities. There have been
case reports of CCB overdose that have
been successfully treated with
Levosimendan (Teker et al., 2010).
Levosimendan is an inotropic drug that is
a calcium sensitizer. It enhances cardiac
contraction by improving the use of
837
cytosolic calcium. Dosages used were an
initial loading dose of 2 μg/kg followed by
an infusion at 2 μg/kg/h and continued
for 30 h. Patients had good responses to
therapy. There have also been good
results from intralipid infusions. For
severe cardiovascular shock that is
unresponsive to standard therapy, there
have been case reports of the use of
peripheral cardiopulmonary bypass to
treat the diseased myocardium, along
with continuous veno-venous
hemofiltration (CVVH) and plasma
exchange therapies (Baud et al., 2007).
Use of MARS has also been shown to be
effective (DePont, 2007).
Nitrates. Nitrates and nitrites are drugs
that produce venous dilation. They can also
cause methemoglobinemia. Common drugs
are nitroglycerin, isosorbide nitrates, amyl
nitrate, sodium nitrate, and ammonium
nitrate.
Nitrates pharmacology. Nitrates and
nitrites cause venous smooth muscle
relaxation at lower doses and can produce
arterial dilation at higher doses. These
effects can cause profound hypotension.
Toxicity can be caused by inhalation, oral
ingestion, and dermal absorption.
Methemoglobinemia can also result in
838
overdose, which converts hemoglobin to
methemoglobin and decreases
oxygen-carrying capacity and delivery to
tissues.
Nitrates symptoms of overdose.
Hypotension and tachycardia are common
effects with ingestion. Cardiovascular side
effects can include cyanosis, dysrhythmias,
syncope, and myocardial infarction. Altered
mental status can occur with seizures. Toxic
doses are between 200 and 1200 mg of
nitroglycerin-containing substances. Toxic
dose of sodium nitrate is usually 1 g, and 10
cc of amyl nitrate can produce significant
levels of methemoglobin. Nausea, vomiting,
abdominal pain, and diarrhea can also
occur. Headache is common. Dyspnea and
decreased pulse oximetry can occur with
methemoglobinemia.
Nitrates diagnostic testing and
monitoring. Monitoring should include
serum electrolytes and ABGs with
co-oximeter because of inaccuracy of pulse
oximetry due to methemoglobin. In cases of
amyl nitrate toxicity, methemoglobin levels
should be monitored. Levels less than 3%
are nontoxic. Frequent monitoring should
include CBC, chemistry panel, and ABGs.
Arterial oxygen (PaO2) and oxygen
saturation levels may be normal despite
significant hypoxia and
methemoglobinemia.
839
Nitrates antidotes/binding agents/
treatment. Gastric lavage and charcoal
administration can be done in cases of
overdose within 1 h. Treatment of
cardiovascular effects is supportive with
oxygen therapy, IV access, IV crystalloids,
use of inotropic medications for
hypotension not responding to fluids, and
continuous ECG monitoring. In cases where
methemoglobinemia develops, treatment
with methylene blue may be needed. If
significant CNS symptoms, hypoxia, or
cardiac instability is present, administration
of 1–2 mg/kg IV can be given over 5 min.
Methemoglobin levels should be repeated
and if they are still elevated and the patient
remains symptomatic, the dose can be
repeated at 0.5–1 mg/kg IV. Methemoglobin
levels should continue to be monitored until
decreasing levels are seen for at least 6 h. In
patients with G-6-PD deficiency, hemolysis
can occur and use of methylene blue is
contraindicated.
Clinical Pearls—Nitrates
If indicated, use a vasopressor with less
beta effects because of the increased
sympathetic outflow with vasodilator
toxicity and resulting tachycardia and
increased myocardial contractility. For
840
life-threatening methemoglobinemia that
is not responding to methylene blue,
exchange transfusion has been used.
Digitalis. Digitalis is a cardiac glycoside,
derived from foxglove plant and is used for
the treatment of systolic heart failure and
rate control. Usually toxicity is caused from
acute or accidental overdose or from other
disease conditions such as acute renal
failure, dehydration, and concurrent
medications that potentiate digoxin,
including paroxetine, rifampin, verapamil,
diltiazem, tetracycline, and erythromycin.
Digitalis pharmacology/symptoms of
overdose. Digoxin inhibits the
sodium–potassium adenosine
triphosphatase pump, which causes
decreased atrial ventricular nodal
conduction and increased cardiac
contractility. It is absorbed in the serum
over 6 h but patients become symptomatic
once tissue levels increase and serum levels
start to decrease. It is excreted renally.
Symptoms of overdose include AV block
with bradycardia, junctional tachycardia,
ventricular tachycardia and fibrillation,
nausea, vomiting, CNS effects,
hyperkalemia, and visual disturbances such
as yellow-green halos.
841
Digitalis diagnostic testing and
monitoring. Serum digoxin levels are
considered toxic if greater than 2.0 ng/ml.
However, levels will be falsely elevated
within 6 h of dosing and may not clinically
correlate with symptoms. Acute overdose
symptoms usually occur after 6 h, and for
patients on chronic doses, toxicity can occur
up to 5 days later. Serious arrhythmias
usually occur within 24 h. Drug levels
should not be relied upon for diagnosis.
Diagnosis should be based on history and
symptomology as patients can be toxic at
therapeutic doses and asymptomatic at high
doses. Patients will need continuous ECG
monitoring, serial electrolytes, 12-lead ECG
monitoring, renal function, oxygen
saturation, ABGs, and chest radiographs. If
symptoms are severe, advanced life support
measures should be instituted along with
administration of Digibind. ECG changes
seen with digoxin toxicity are sinoatrial
nodal dysfunction, prolonged PR intervals,
short QT interval, and sloping of the ST
segment. Tachycardia or heart block can
occur from the suppression of the sinoatrial
node and increased automaticity with
decreased conduction at the AV node.
Digitalis antidotes/binding agents/
treatment. Charcoal can be used if time of
overdose is known. Hydration in the setting
of dehydration and acute kidney injury
842
should be initiated with D5NS or normal
saline infusion. Atropine is first-line therapy
for bradyarrhythmias that are symptomatic.
Indications for Digibind include cardiac
instability with ventricular arrhythmias or
severe heart block, hyperkalemia with
potassium levels greater than 5 mEq/l, and
digoxin levels greater then 15 ng/ml
regardless of symptoms. Digibind is given at
a dose based on the total body level of
digoxin taken 6 h after ingestion. The
general rule is that 38 mg of Digibind (one
vial) will bind 0.5 mg of digoxin and 40 mg
of Digifab (one vial) will bind 0.5 mg of
digoxin. If cardiac instability and arrest are
imminient, Digibind may be given as a bolus
dose; otherwise, it should be infused over 30
min. Lidocaine is usually not effective for
ventricular arrhythmias. Phenytoin is the
drug of choice for ventricular arrhythmias
due to increase in the ventricular fibrillation
threshold and enhanced conduction through
the AV node. IV magnesium can also be
given to stabilize cardiac function. Chronic
overdose symptoms may be different from
acute toxicity with symptoms of nausea,
vomiting, and anorexia. CNS effects are
common as are yellow and green halos and
other altered color perceptions. Levels may
be therapeutic or only minimally elevated. If
patients are on diuretics, hypokalemia and
hypomagnesemia can induce toxicity.
843
Clinical Pearls—Digitalis
Common causes of digoxin toxicity
outside of intentional overdose are
dehydration and acute kidney injury.
Usually with hydration and improvement
of renal function, digoxin levels improve.
If Digibind is given, trending the digoxin
level is not accurate and will be
abnormally high. Testing for a free level of
digoxin may be helpful but this is usually
a send-out test in most hospitals and the
results may take several days. Avoid
calcium as this may potentiate cardiac
toxcity because digoxin increases
intracellular calcium. Hyperkalemia
should be treated with regular insulin,
dextrose 50, hydration, and Kayexalate
15–30 g by mouth four times a day (each 1
g in exchange for 1 mEq of potassium).
Reoccurance of toxicity may develop in
patients with acute renal failure or on
dialysis. Patients should have a renal
consult and may need to have dialysis
done in a timely fashion. Toads from the
Bufonidae family also secrete a toxin from
their glands in their skin, which contains
cardiac glycoside properties, that is added
to some natural medications from the Far
East. This acts as an aphrodisiac. Some
844
people also practice licking of these frogs
to get high (Garg, Hippargi, and
Gandhare, 2008). Digibind has not shown
to be effective in these situations (Leitch,
Lim, and Bora, 2000).
Table 13.5 Overdose of beta blockers: effects
and treatment.
Name
Receptor Lipid
Half-life Elimination M
site: β1
solubility
ca
or β2
ef
ov
Metoprolol β 1
High
3–4 h
Hepatic
Br
hy
H
Atenolol
β1
Low
6–9 h
Renal
Br
H
845
Name
Receptor Lipid
Half-life Elimination M
site: β1
solubility
ca
or β2
ef
ov
Carvedilol β1, β2,
and a1
High
6–10 h
Hepatic
Co
br
hy
Nadolol
β1 and β2 Low
14–24 h
Renal
AV
co
fa
Labetalol
β1 and β2 Low
3–6 h
Hepatic
H
br
Sotalol
β1 and β2 Low
5–12 h
Renal
De
pr
To
H
ta
Ve
ta
Pr
in
Esmolol
β1
Low
15 min
H
Br
Acebutolol β1
Moderate
3–6 h
Renal
Be
ef
Se
846
Name
Receptor Lipid
Half-life Elimination M
site: β1
solubility
ca
or β2
ef
ov
Betaxolol
β1
Low
14–22 h
Hepatic
Propanolol β1 and β2 High
3–5 h
Hepatic
Co
br
Clonidine
6–24 h
Hepatic
CN
co
Central
acting
alpha
adrenergic
agonist
M
br
H
Note: IV calcium, glucose, high-dose insulin
and potassium therapy can be considered for
refractory hypotension in beta blocker
overdose/calcium channel overdose. May also
consider intravenous lipid emulsion (ILE) for
refractory treatment of symptoms with
cardiovascular collapse (Cave, 2011). Consult
with local Poison Control Center.
Antiarrhythmic agents
These are agents that exert action on the heart
and can be very toxic with life-threatening
847
consequences in cases of overdose and toxicity.
There are several classes of antiarrhythmic
agents that are classified based on the
Vaughan–Williams classification system. Type 1
drugs inhibit fast sodium channels and cause
cardiac cell depolarization and impulse
conduction
abnormalities,
depressing
myocardial functioning and contractility. Type
1a and 1c also block potassium channels and
toxicity creates problems with depolarization
and conduction in the cardiac cycle. This
frequently prolongs QT intervals. Drugs such as
flecainide and propafenone are Type 1c cardiac
drugs and can cause prolongation of the QRS
complex in overdose. Type 1b drugs, such as
phenytoin and lidocaine, block sodium
channels but have no effect on the QRS
complex. Class II drugs are generally classified
as beta blockers and block beta-adrenergic
receptors. Type III cardiac arrhythmic agents
are potassium channel blockers such as
bretylium and Sotolol. Prolongation of
potassium channels causes increased duration
of the action potential and prolongs the
refractory period. Class IV antiarrhythmics are
classified as CCBs and slow the influx of
calcium through cellular calcium channels.
They primarily act on vascular smooth muscle
and the heart. All drugs in this section are
widely distributed to body tissues. These drugs
usually have a narrow therapeutic index and
may show toxicity even at therapeutic doses.
Ingestion of twice the recommended dose can
848
produce significant toxicity except in the case of
amiodarone,
which
has
an
extensive
distribution to tissues.
Potassium blockers. Antiarrhythmic
drugs that interfere with conduction
through potassium channels include drugs
such as amiodarone, bretylium, and sotolol.
Pharmacology. Potassium blockers block
potassium channels by prolonging action
potentials and the refractory period, which
in turn prolongs the QT interval.
Amiodarone
possesses
noncompetitive
beta-adrenergic blocking effects, which are
very similar to calcium channel blocking
effects. Amiodarone can frequently cause
bradyarrhythmias,
negative
inotropic
effects, pulmonary fibrosis, and hyper/
hypothyroidism. Amiodarone is a drug that
is extensively distributed throughout the
tissues and even massive single doses
produce mild toxicity. It is an iodine-based
compound that is similar in structure to
thyroxine. Large doses can also cause iodine
toxicity. Half-life can be up to 50 days.
Sotalol has beta-adrenergic properties along
with Class III antiarrhythmic activity.
Overdosages are usually dose-dependent
and can cause Torsades de pointes and
ventricular fibrillation. Significant QTc
prolongation can occur. Absorption is
generally 1–4 h but can be longer with
849
sustained-release formulas. See Table 13.6
for drugs that cause QT prolongation. See
also Chapter 4.
Symptoms of overdose. Symptoms
depend on the specific drug and half-life.
Symptoms can include QT/QTc
prolongation, bradyarrhythmias, AV blocks,
and hypotension. Cardiogenic shock can
occur. Neurological symptoms can include
altered mental status.
Diagnostic testing and monitoring.
Diagnosis is based on history. There are no
specific tests that can detect overdose.
Depending on the agent ingested, drug
levels may be available but treatment should
not be delayed. Patients with suspected
overdose of these substances should be
admitted to a critical care unit with
continuous ECG monitoring and frequent
monitoring of QT and QTc intervals for a
minimum of 24 h if toxicity is present. Serial
12-lead ECGs should be monitored.
Supplemental oxygen, IV access,
administration of IV crystalloids, and
vasopressors may be needed. CBC, LFTs,
and electrolyte monitoring with calcium and
magnesium should be assessed. ABGs
should be monitored. Thyroid panel may be
useful with amiodarone ingestions.
Frequent neurological monitoring for coma
and seizures should also be done.
850
Antidotes/binding agents/treatment.
In cases of overdose within 1 h, gastric
lavage and charcoal can be used. Laxatives
may be needed for sustained-release
formulas. Protect airway, breathing, and
circulation. For arrhythmias do not treat
Type 1a, Type 1c, or Type IIIc overdose with
Type 1a drugs (Olsen, 2005). Administration
of sodium bicarbonate for hypotension,
arrhythmia, and QRS prolongation at
dosages of 1–2 mEq/kg is usually effective.
Treat seizures with benzodiazepines.
Clinical
Pearls—Antiarrhythmics
Dialysis or hemoperfusion is usually
ineffective due to extensive tissue
distribution.
Sodium channel blockers are Class IA,
IB, and IC drugs. Class IA prolongs the QRS
and QT intervals. Class IB agents shorten
the action potential and have less effect on
the fast sodium channels so there is little
effect on the QRS, QT, and PR intervals.
Class IC drugs decrease conduction and
have potent sodium channel blockade,
which increases the QRS interval more than
the other Class 1 agents (Ling, 2001). These
are drugs that block fast sodium channels.
851
Examples of Class IA drugs are Norpace,
procainamide, and quinidine. Some
examples of Class IB antiarrhythmics are
Dilantin, lidocaine, mexiletine, and
tocanide. Examples of Class IC are flecainide
and propafenone.
Sodium channel blockers symptoms
of overdose. General symptoms of
overdose usually affect the cardiovascular
system and include hypotension,
bradycardia, widened QRS, Torsades de
pointes, and prolongation of the QT interval.
Class IC usually causes negative inotropic
effects. Flecainide can also cause
neutropenia, hypotension, AV blocks, and
asystole due to the prolongation of the QRS
and QT intervals. Lidocaine toxicity usually
causes CNS symptoms, with confusion and
agitation being the most common. Tocainide
and mexiletine overdose can cause CNS
alterations such as confusion, sedation, and
coma.
Sodium channel blockers diagnostic
testing and monitoring. Serum levels
are available for most drugs in this class but
treatment should not be delayed waiting for
levels. Patients should be admitted to a
critical care unit with continuous ECG
monitoring and 12-lead serial ECG
monitoring to assess for QRS prolongation
and QTC prolongation.
852
Sodium channel blockers antidotes/
binding agents/treatment. In cases of
overdose within 1 h, gastric lavage and
charcoal can be used. Laxatives may be
needed for sustained-release formulas.
Sodium bicarbonate infusion 1–2 mEq/kg
IV is used in the setting of sodium channels
overdose and QRS widening.
Clinical Pearls—Sodium
Channel Blockers
Drugs such as cocaine, Benadryl, TCAs,
phenothiazines, and Tegretol have
sodium-blocking principles but are not
classified as antidysrhythmics. Dialysis
may be benefical in tocanide or flecainide
overdose.
Table 13.6 Drugs that cause prolonged QT
interval (not all inclusive).
Arsenic
Droperidol Organophosphates
Atypical
antipsychiotics
Erythromycin Phenothiazines*
Citalopram
Florides
Propoxyphene
Clarithromycin
Haloperidol
Scorpion or spider
bite
Class Ia
Hypo Mg, K,
antidysrhythmics CA
853
Tamoxifen
Arsenic
Droperidol Organophosphates
Class III
Lithium
antidysrhythmics
Bactrim
Contrast
injection
Tricyclic
antidepressaants
Octretide
*Major
phenothiazines
causing
QT
prolongation are thioridazine and thiothixene.
Toxic alcohols
Drug overview
These are substances that are toxic to all body
systems and may be indicated in accidental and
deliberate ingestion. Drugs discussed are
ethylene glycol, propylene glycol, methanol, and
isopropyl alcohol. Most of these alcohols cause
profound metabolic and lactic acidosis. PG has
a relatively low toxicity and the most frequent
cause seen in critical care is IV Ativan toxicity.
Ethylene glycol is a colorless, odorless,
syrupy, sweet-tasting substance that is
found in many household products such as
antifreeze, detergents, deicing products,
paints, hydraulic brake fluids, and other
industrial fluids. Ethylene glycol becomes
toxic after ingestion through its metabolites.
Ingestion is often accidental but there have
been many forensic science cases that have
found deliberate poisoning attempts. The
anion gap acidosis that is produced is due to
854
the accumulation of glycolic, glyoxylic, and
oxalic acid along with hydrogen ion titration
from these. The formation of hippuric acid
ensues and depletion of other cofactors for
the tricarboxylic acid cycle results in an
accumulation of lactic acid (Adler and
Weening, 2006). Osmolar gap is usually
increased first without acidosis, followed by
evidence of toxic metabolites. Alcoholics
have frequently ingested ethylene glycol
substances as an alcohol substitute.
The toxic lethal dose in adults is around 100
ml or (1–1.5 ml/kg). The lethal blood level in
untreated adults is 200 mg/dl. Peak levels
occur 1–4 h after ingestion. It is widely
distributed to the tissues. Blood levels
usually do not correlate with the severity of
illness. Three signs to look for when making
this diagnosis are an elevated anion and
osmolar gap, hypocalcemia, and urinary
calcium oxalate crystals (Scalley et al.,
2002).
Ethylene glycol symptoms of
overdose. Presentation is highly variable
depending on amounts of ethylene glycol
and time of ingestion. Anion gap acidosis
with elevated osmolar gap is usually present
but osmolar gap may be low in late
presentation of ingestion where metabolites
have already been processed by the kidney
(Jammalamadaka and Raissi, 2010).
Toxicity is usually fatal within 24–72 h if
855
untreated. Toxicity may consist of three
phases. The CNS phase consists of ataxia,
confusion, nystagmus, seizures, myoclonic
jerks, coma, and tetany from hypocalcemia.
This usually occurs within the first 1–12 h
after ingestion. GI complaints can occur in
this phase. Ethylene is rapidly absorbed by
the GI system and symptoms include
nausea, vomiting, and abdominal pain. The
second phase or cardiovascular phase
usually occurs within 12–72 h post
ingestion. Symptoms include hypertension,
cardiac arrhythmias, tachycardia,
respiratory difficulty, and hypothermia.
Pneumonitis and ARDS have also occurred.
Cardiac failure may also occur in cases of
significant poisoning and shock. Phase 3 is
the final phase with renal toxicity and
failure. This can occur within 24–72 h after
ingestion and patients develop flank pain
and oliguric renal failure. The metabolite
oxalate causes widespread tissue injury
throughout the body and causes tubular
damage in the kidney that may be
permanent.
Ethylene glycol diagnostic testing
and monitoring. Diagnosis is usually
based on the history of ingestion. There is
specific testing that should be done to check
for toxic alcohol ingestion. Ethylene glycol,
methanol, and PG levels should be drawn.
Testing is usually done at large regional
856
hospital centers and results are usually
available in a matter of hours. If a strong
suspicion of diagnosis exists, treatment
should not be delayed while awaiting
testing. Anion gap acidosis with osmolar gap
is usually present. Oxalate or hippurate
crystals may be present in the urine. Woods
lamp testing can be performed. Antifreeze
contains fluorescein, which gives it a yellow
green color; urine may fluoresce with the
use of a Woods lamp depending on the
concentration and timing of ingestion. CBC,
extended electrolytes, ABGs, serum
osmolarity, drug toxicology panels,
urinalysis, blood ketone levels, LFTs, lactic
acid, and 12-lead ECG should be monitored
every 4–6 h. ECG may show symptoms of
hypocalcemia due to calcium oxalate
crystals and prolonged QTC may occur.
Hyperkalemia may occur in the setting of
acute renal failure. Ethylene glycol levels
should be sent every 12–24 h to monitor
levels during fomepizide and dialysis
treatments. In the setting of osmolar gap
with alcohol ingestion, gap needs to be
corrected for alcohol level. There are many
online medical calculators that will do this.
Ethylene glycol antidotes/binding
agents/treatment. Airway and
circulatory support is usually needed. Treat
hypotension with crystalloids. Vasopressors
may be needed in shock states. Electrolyte
857
replacement may be indicated. Bicarbonate
infusions may also be needed. Treat seizures
with anticonvulsants. Fomepizole is the
treatment of choice for ethylene glycol
toxicity. Fomepizole is an inhibitor of
alcohol dehydrogenase and prevents acidic
ethylene glycol metabolites. The loading
dose is 15 mg/kg followed by 10–15 mg/kg
every 12 h for four doses. Fomepizole is
continued until ethylene glycol levels are
less than 20 mg/dl. If fomepizole is not
available, ethanol infusion can be used. The
dosage is 10% ethanol diluted in 5%
dextrose and infused at 1.4–2 ml/kg/h after
a loading dose of 8–10 ml/kg over 30 min.
Ethanol is very toxic to the veins and central
access may be needed. Hemodialysis can be
used to remove ethylene glycol and its
metabolites. Indications for use are severe
metabolic acidosis with renal dysfunction
and ethylene glycol levels greater than
25–50 mg/dl and continued until levels are
less than 10 mg/dl. Dosing of fomepizole
needs to be adjusted when receiving dialysis.
Clinical Pearls—Ethylene
Glycol
Many substances can elevate the anion or
osmolar gap but only diabetic ketoacidosis
(DKA), alcoholic ketoacidosis, ethylene
858
glycol, and methanol elevate both. False
positive levels of ethylene glycol can occur
in patients who have high triglyceride
levels and elevated levels of
2,3-butanediol, which may be present in
chronic alcoholics and with ingestion of
other glycols. In the setting of coingestion
of alcohol and ethylene glycol, alcohol
levels will be decreased. For differential
diagnosis, think of the mnemonic
“METAL ACID GAP.”
M—methanol, metformin
E—ethylene glycol
T—toluene (glue)
A—alcohol ketoacidosis
L—lactic acidosis
A—aspirin
C—carbon monoxide, cyanide
I—iron, Isoniazoid
D—DKA
G—generalized seizures
A—aminoglycoside agents
P—paraldehyde, phenformin
Methanol drug overview. This is a toxic
alcohol that is clear, colorless, and has a
859
slight alcoholic odor. It is generally found in
industrial solvents, canned solid fuels
(sternos), windshield washer fluid, glass
cleaners, and octane boosters. Toxicity can
occur through ingestion, inhalation
(carburetor cleaner), and absorption
through skin (Givens, Kalbfleisch, and
Bryson, 2008). Methanol is rapidly
absorbed through the GI system and
symptoms of intoxication can occur within 1
h. Lethal dosages vary among patients but
are usually between 30 and 240 ml. Peak
blood levels usually occur 30–90 min after
ingestion. Methanol converts to toxic
formaldehyde and formate acid in the liver
and causes metabolic acidosis. Formate acid
is the cause of most of the serious effects of
methanol toxicity including ocular edema
and resulting blindness. Lactic acid occurs
due to hypotension and tissue hypoxia from
anaerobic glucose metabolism.
Methanol diagnostic testing and
monitoring. Methanol drug levels should
be obtained. Toxic levels are usually greater
than 50 mg/dl and acidosis is usually
present. Peak levels less that 20 mg/dl are
usually asymptomatic. Levels greater than
150 mg/dl are usually fatal. Anion gap
acidosis is present with osmolar gap.
Laboratory monitoring and supportive
measures are the same as ethylene glycol
treatment.
860
Methanol symptoms of overdose.
Early symptoms may include nausea,
vomiting, and hemorrhagic gastritis. Vision
deficits such as blurred vision or “snowfield
blindness” (complaints of peering through a
snowstorm) may occur. CNS effects are
common with confusion and ataxia effects.
Respiratory depression, seizures, and coma
can occur. Hyperthermia or hypothermia
can be present. Hyperemia and retinal
edema may be present. Other symptoms are
similar to ethylene glycol poisoning.
Methanol antidotes/binding agents/
treatment. Treatment is the same as
ethylene glycol. Fomepizole and dialysis
should be initiated before visual
disturbances occur. Mortality is 20% despite
treatment and many patients are left with
permanent ocular damage. Dialysis is
usually indicted with ocular findings, severe
electrolyte disturbances, and levels greater
than 20 mg/dl.
Clinical Pearls—Methanol
When methanol is coingested with
ethanol, ethanol inhibits conversion of
toxic metabolites, which cause metabolic
acidosis and thus an elevated osmolar gap
may be present without an elevated anion
gap.
861
Isopropyl alcohol drug overview.
Isopropyl alcohol is usually found in
substances such as rubbing alcohol, glues,
nail polish remover, and in many industrial
solvents. Toxic doses are usually 2–4 ml/kg.
Isopropyl is an alcohol that, if ingested
orally, causes significant CNS depression.
Isopropyl is excreted in the urine unchanged
and 50% is metabolized by the liver to
acetone. Acetone is nontoxic and is readily
excreted by the kidney. No toxic metabolites
are produced. Metabolic acidosis should not
occur unless there are signs and symptoms
of poor perfusion and organ damage from
hypotension.
Isopropyl alcohol symptoms of
overdose. Symptoms are similar to alcohol
ingestion but more severe as isopropyl is
twice as potent. Symptoms generally affect
the CNS with ataxia, slurred speech, coma,
respiratory depression, or arrest.
Hypotension and myocardial depression can
occur from profound vasodilation. Gastritis
and GI bleeding can also occur.
Hypoglycemia and positive osmolar gap may
also be present. Levels of more than 150
mg/dl usually cause coma and hypotension
and levels over 200 mg/dl are not
compatible with life. Maximal distribution
occurs within 2 h (Jammalamadaka and
Raissi, 2010).
862
Isopropyl alcohol diagnostic testing
and monitoring. Treatment is supportive.
Laboratory testing should consist of CBC,
ETOH levels, extended chemistries, and
ECG monitoring. Serum osmolarity and
ABGs should be monitored. Support of the
airway may be needed due to the respiratory
effects of the isopropyl, and fluid
resuscitation may be needed to support the
circulatory system. Isopropyl levels can be
drawn and are usually a send-out test with
other toxic alcohols.
Isopropyl alcohol antidotes/binding
agents. Charcoal is generally not effective
due to rapid absorption of isopropyl by the
GI tract. Overdose has frequently been seen
in coingestions. There is no specific
antidote.
Clinical Pearls—Isopropyl
Alcohol
The hallmark of isopropyl poisoning is
ketosis with no acidosis, caused by
acetone. Isopropyl can also produce
elevated alcohol levels with an increased
lactate and lactate dehydrogenase levels.
Propylene glycol drug overview. PG is
classified as an alcohol and is a viscous,
colorless drug diluent that is used in various
863
drug compounds to stabilize unstable drugs.
IV solutions of lorazepam, valium,
etomidate, nitroglycerin, trimethoprim,
sulfamethoxazole, and Dilantin all contain
various amounts of PG. Lorazepam has the
highest concentration of PG per milliliter.
Lorazapam vials, both 2 and 4 mg/ml,
contain 0.8 ml (830 mg of PG) (Yaucher et
al., 2003). The World Health Organization
recommends a maximum dose of 25 mg/kg/
day of PG (Neale et al., 2005). PG can cause
adverse iatrogenic effects when
administered in moderate to high doses and
in some case reports has significant
metabolic acidosis in minimal doses (4–6
mg/h) over short periods of time (Cawley,
2011).Hydrophobic drugs are mixed with PG
to stabilize them and produce liquid
formulations for drug administration. Drug
half-life varies from 1.4 h at low doses to 3.3
h at higher doses. Drug clearance decreases
at higher doses and 45% of an administrated
dose is eliminated unchanged by the kidney.
The remaining amount is metabolized by
hepatic alcohol dehydrogenase, then to
dl-lactaldehyde or methylglyoxal. This
converts to dl-lactate and then to d-lactate.
Because d-lactate clears slowly from the
body, an excessive accumulation produces
significant CNS symptoms from
accumulation in the brain and elevated
lactic acid levels in the blood. Patients with
864
existing renal or hepatic dysfunction are at
increased risk (Neale et al., 2005).
Propylene glycol symptoms of
overdose. PG has a relatively low toxicity.
Patients have signs and symptoms of
metabolic acidosis with positive anion and
osmolar gap. Osmolar gaps higher than 10
can cause acute tubular necrosis in the
kidney. Patients with renal insufficiency
have a higher risk. Patients may have lactic
acidosis.
Propylene glycol diagnostic testing
and monitoring. PG levels can be sent for
study. Elevated levels may not correlate with
toxicity. If diagnosis is suspected,
monitoring should include serial extended
chemistries, serum osmolarity, and lactic
acid until levels normalize.
Propylene glycol antidotes/binding
agents/treatment. Discontinuation of
PG-containing medications is
recommended. Care is supportive. Sodium
bicarbonate may be helpful. There is no
indication for fomepizole. Dialysis may be
helpful but is usually not indicated.
865
Clinical Pearls—Propylene
Glycol
The risk of PG toxicity increases with
moderate to large doses of medications
containing this diluent and also with a
combination of drugs that contain PG.
Anticholinergics/Cholinergics/
Antihistamines (ACA)
Drug overview
Antihistamines are drugs that are usually found
in OTC medications for motion sickness, cold,
and allergy symptoms. Examples of H1 receptor
antagonists
include
diphenhydramine.
Loratadine is a newer nonsedating H1 blocker
that is peripherally selective. Peripherally
selective antihistamines have a lower affinity to
alpha-adrenergic and cholinergic receptor sites
and cause fewer symptoms of dry mouth,
flushing, CNS depression, and tachycardia.
Anticholinergic activity is present in drugs that
contain
antihistamines,
antispasmodics,
skeletal muscle relaxants, and TCAs. Specific
plants may also contain anticholinergic
alkaloids. There are many types of
antihistamines (six structural classes) and
anticholinergic drugs, which are impossible to
cover in this brief summary. In the United
866
States, calls to Poison Control Centers in 2008
accounted for 3.6% of exposures to H1 and H2
antihistamine antagonists. Diphenhydramine
was the most common exposure (French and
Tarabar, 2010).
Anticholinergic agents antagonize acetylcholine
at central and muscarinic receptors. Inhibition
of muscarinic receptors can lead to cardiac
effects such as rapid or slow heart rate in the
case of cholinergic agents. Glands that are most
affected are exocrine glands (salivation and
sweating). Smooth muscle is also affected.
Antihistamines with H1 effects antagonize
histamine at H1 receptor sites. First-generation
H1 blockers (e.g., Benadryl) differ from
second-generation H2 blockers (e.g., Zyrtec) in
their neurotransmitter blockade in the CNS. H1
blockers block 50–90% of H1 receptors in the
brain as opposed to 30% with Zyrtec (Simons,
2004). Certain H1 antagonists can also block
fast sodium channels, which can cause cardiac
conduction delays, dysrhythmias, and widening
of the QRS. H2 antihistamines inhibit gastric
acid secretion and usually do not produce toxic
effects in overdose. The antihistamine drugs
without anticholinergic effects are nonsedating.
Loratadine (Claratin), a second-generation H1
blocker, is the most closely related to the
anticholinergics.
Diphenhydramine,
a
first-generation H1 blocker, has local anesthetic
effects, depresses the CNS, and can cause
sedation. It can also cause profound agitation
867
and prolonged
QRS at high doses.
Rhabdomyolysis and acidosis have been
reported from seizure activity. Dystonic
reactions can occur. Absorption can be delayed
with
anticholinergic
and
antihistamine
overdose due to the effect of decreased gastric
motility. Cholinergics cause rapid gastric
motility and the range of toxicity is variable
based on the drug ingested. Generally, in
antihistamine overdose, the toxic dose is three
to five times the daily dose. Peak plasma effects
can range from 3 to 24 h and metabolism
occurs in the liver.
ACA symptoms of overdose
Diagnosis is based on the history of ingestion
and symptoms of anticholinergic toxidrome,
which include flushing, hyperthermia, dilated
pupils, and various CNS symptoms ranging
from anxiety and agitation to delirium. There is
a broad range of differential diagnosis. Urinary
retention and intestinal ileus can occur.
Tachycardia, arrhythmias, hypertension, and
cardiogenic shock have been reported and are
more common in the antihistamines with
prominent anticholinergic effects. Pulmonary
edema can occur due to cardiovascular failure.
Rhabdomyolysis has been reported with
doxylamine ingestion of greater than 20 mg/kg.
868
ACA diagnostic testing and monitoring
Drug levels are generally not available.
Monitoring of ECG, CBC, CPK, extended
chemistries, LFTs, ABGs, and serial 12-lead
ECGs should be conducted. CT scan of the head
may be needed to rule out any other central
process. Drug screenings should be done for
coingestion of other substances.
ACA antidotes/binding agents/treatment
Care is supportive with maintenance of airway,
breathing, and circulation. Activated charcoal
and gastric lavage can be administered if within
1 h of ingestion. For profound CNS effects such
as agitation, seizure, or coma, intubation may
be necessary. IV crystalloid fluids should be
administered and benzodiazepines given for
any
seizure
activity
and
agitation.
Physostigmine can be given as long as there are
no cardiac abnormalities such as PR and QRS
prolongation on ECG. Physostigmine is an
acetylcholinesterase inhibitor that binds to
acetylcholinesterase and reverses central and
peripheral symptoms. It is indicated only with
symptoms of single anticholinergic exposure,
pronounced CNS effects that are unresponsive
to benzodiazepines, seizures that are not
responsive to other treatments, and absence of
ECG changes to the PR and QRS complex.
Dosage is 0.5–1 mg by slow IV infusion over 5
min; effects are usually seen within 3–5 min. A
repeat dosage can be given within 10 min if
869
needed to a total dose of up to 4 mg. For
antihistamine toxicity with QRS prolongation,
sodium bicarbonate can be used at 1–2 mEq/kg
IV. Dialysis is not effective.
Clinical Pearls—ACA
Asians are much less sensitive to
diphenhydramine (Benadryl) due to their
increased acetylation to a nontoxic
metabolite when overdose is present. The use
of physostigmine should be avoided in
patients with TCA overdose as it may cause
asystole, AV blocks, and seizures.
Anticonvulsants
Drug overview
Anticonvulsants are a group of drugs that are
used to treat seizures. They may also be used in
chronic pain syndrome, migraines, and bipolar
disease. Anticonvulsants work by raising the
seizure threshold. They function in the CNS by
inhibiting or decreasing excitatory tone.
Anticonvulsants such as gabapentin and
levetiracetam have an unknown mechanism of
action. Toxicity from anticonvulsants can be
either acute or chronic.
In the CNS, glutamine is present as a
neurotransmitter that produces excitation
870
through sodium channels and the NMDA
receptors. Sedation happens in the CNS
through
GABA
neurotransmitters
and
receptors. Anticonvulsants generally work on
these receptors. Some also block calcium
channels.
Anticonvulsants symptoms of overdose
Diagnosis is usually based on history. Most
anticonvulsants affect the CNS through
sedation,
lethargy,
confusion,
agitation,
nystagmus, or ataxia. Coingestions with other
drugs are common. Carbamazepine can cause
cardiac dysrhythmias, respiratory depression,
coma, and seizures at toxic levels greater than
16 μg/ml. The clinical picture of toxicity may
not correlate with levels ingested (Yildiz et al.,
2006). Lamotrigime can cause hypersensitivity
reactions and multisystem organ failure (Wade
et al., 2010). Phenytoin can cause cardiac
arrhythmias. It is classified as a Class IB
antidysrhythmic. Toxic cardiac doses have not
been reported with oral dosage but have
occurred with IV dosing. Hypotension,
bradycardia, and cardiac arrest have occurred.
Levetiracetam (Keppra) can cause significant
agitation, aggression, and altered level of
consciousness, which can lead to coma;
intubation may be needed. Valproic acid can
cause thrombocytopenia and metabolic acidosis
with severe toxicity and has caused respiratory
failure but most symptoms are mild. Toxic
871
symptoms can occur in ingestions grater than
400 mg/kg (Isbister et al., 2003). Drug levels
are available on certain drugs such as
phenytoin, carbamazepine, valproic acid, and
levetiracetam but may require send-outs to
outside agencies. Elevated ammonia levels may
also be present with valproic acid overdose but
it generally does not produce hepatic toxicity or
CNS symptoms.
Anticonvulsants diagnostic testing and
monitoring
Patients should be admitted to critical care if
signs and symptoms of CNS or cardiac toxicity
are present. Depending on symptoms, agent
used,
and
sustained-release
formulas,
monitoring may be needed for a minimum of 24
h. Drug levels should be drawn if testing is
available. Coingestions should be considered
and tested for. Continuous ECG monitoring,
level of consciousness, CBC, extended
electrolytes, LFTs, and ABGs should be
monitored.
Anticonvulsants antidotes/binding agents
There are no specific antidotes. Care is
supportive. Administration of charcoal and
gastric lavage may be used if ingestion is within
1 h. Whole-bowel irrigation may be needed with
enteric forms of medications. Caution should be
used in patients with active seizure disorders
when lowering toxic levels so seizures are not
872
precipitated. If seizures are precipitated, use of
benzodiazepines should be the first-line
therapy. Bicarbonate can be administered for
severe metabolic acidosis.
Clinical
Pearls—Anticonvulsants
There have been case reports in valproic acid
overdose of the use of hemodialysis and
high-volume hemofiltration (Licari et al.,
2009). Hemodialysis has also been effective
in gabapentin, levetiracetam, and topiramate
overdose but is rarely needed and should be
reserved for severe symptoms of hypotension
and seizures with metabolic acidosis that is
refractory to other supportive therapies.
Acute carbamazepine overdose has also been
treated with prolonged hemoperfusion and
hemodialysis (Ozhasenekler et al., 2012;
Peces et al., 2010). There have also been case
reports of naloxone being effective in valproic
acid overdose (Roberge and Francis, 2002).
Common toxidromes and
treatments for poisoning
conditions
A toxidrome is a word that describes a certain
common group of symptoms related to a drug
873
class. Generally, the label toxidrome is related
to an overdose of this drug class. Symptoms are
generally similar and use of the toxidrome
facilitates rapid diagnosis and treatment for
toxic overdose (Table 13.7).
Table 13.7 Common drug or toxin overdose
and antidotes.
Drug
Antidote
Antidote
dosages
M
ov
sy
Acetaminophen
Mucomyst
either IV or po
IV load with 150
mg/kg/15 min,
followed with 50
mg/kg for 4 h,
then 100 mg/kg
for 16 h
De
of
ini
up
874
Drug
Antidote
Beta blocker
Glucagon
Calcium channel blocker
Antidote
dosages
M
ov
sy
5–15 mg IVP:
Br
may be followed sin
by infusion if
needed
Calcium
High-dose
Hy
calcium
gluconate or
chloride 1–3 g IV
bolus, then
20–50 mg/kg/h
High-dose
insulin and
glucose
High-dose
insulin 0.5–1
u/kg/h with
dextrose
infusion
Ca
co
be
Consider ILE in Atropine 0.5–1
refractory
mg IVP
shock
Anticholinergics
Physostigmine
0.5–1 mg IV
HT
tac
ur
Ps
ag
de
875
Drug
Antidote
Antidote
dosages
M
ov
sy
Botulism
Botulism
antitoxin
1–2 vials
Pr
sy
de
pa
Deferoxamine
indicated with
shock and
hemodynamic
instability
Initial dose is 15 Sy
mg/kg/h, can
de
titrate to 40 mg/ tox
kg/h
INH (isoniazid)
Vitamin B6
(Pyridoxine)
Usual dose: for
each gram of
INH ingested
give gram of B6
Arsenic/mercury
DMSA
GI
he
D-penicillamine
Ca
sh
Iron
Tricyclics
876
Need to obtain
from specific
state of federal
agencies
Major side effect
is hypotension
Sodium
bicarbonate IV
magnesium for
Torsade de
pointes
D5W with 2–3
amps
bicarbonate at
75–100 cc/h
Experimental
ILE therapy
1–2 g IVP
Se
EC
OR
se
Drug
Antidote
Antidote
dosages
M
ov
sy
Opiates
Naloxone
0.4 mg IVP can
be repeated
every 2–4 min
for a maximum
dose of 2 mg
Re
de
hy
Methotrexate
Folate,
leucovorin
calcium (give
within 1 h of
posioning)
Folic acid 15 mg GI
po/IV q6 h until he
methotrexate
inj
level is nontoxic
Flumazenil
0.1–0.2 mg IV to Se
maximum of 2
fro
mg
Benzodiazepines
877
Leucovorin dose
is equal to or
greater than
methotrexate
dose given IV,
further doses
should be guided
by methotrexate
levels
Drug
Antidote
Calcium channel
blockers
Calcium
gluconate
Antidote
dosages
M
ov
sy
Patients may
Br
need large doses hy
up to 10 g IV
hy
an
Calcium cloride 5–15 mg IVP
Glucagon
0.5–1 mg IV to
maximum dose
of 10 mg
Atropine
Cyanide
Amyl nitrate,
Cyanide antidote Br
sodium nitrate, kit
hy
thiosulfate
ag
Goal is to obtain Ch
a
methemoglobin
level of 20–30%
High-flow
oxygen
Methemoglobin-forming Methylene blue 1–2 mg/kg IV
agents/conditions
over 3–5 min,
can repeat 1 mg/
kg if symptoms
not resolved
Cy
un
ox
No
sa
Ch
blo
878
Drug
Antidote
Antidote
dosages
Organophosphates
Atropine,
pralidoxime
(2-PAM)
1 mg initially,
Br
then can be
hy
repeated to treat
drying of oral
secretions
Carbamates
Atropine
2-PAM 1–2 g IV, SL
may repeat or
mn
start drip for
continued
muscle weakness
Methanol
Ethanol,
fomepizole,
folate,
leucovorin
Fomepizole 15
Se
mg/kg loading
ac
dose, |then 10
or
mg/kg over 12 h
× 4 doses, then
15 mg/kg over 12
h until methanol
<20 mg/dl
879
M
ov
sy
Drug
Antidote
Antidote
dosages
Ethylene glycol
Ethanol,
fomepizole,
pyridoxine
Folate and
thiamine
coadministration
for cofactor
support
M
ov
sy
Folate 50–70 mg
IV over 4 h × 24
h, then oral
doses can be
given until
resolution of
symptoms
Thiamine 100
mg IV over 6 h
for 2 days
Pyridoxine 50
mg IV for 6 h for
2 days
Lead
DMSA
chelator/
succimer
10 mg/kg or 350 An
mg/m2 tid for 5 vo
days then bid for ab
ne
14 days
sy
Coumadin
Vitamin K
5–10 mg po/IV
daily until INR
normalizes
FFP
880
Bl
Drug
Antidote
Heparin
Protamine 1
mg/100 units of
heparin
Hypoglycemic agents,
insulin
D50, dextrose
Antidote
dosages
M
ov
sy
Bl
0.5–1 amp D50
IV repeated as
needed for low
blood sugar
Co
Infusion of
Hy
dextrose/D50 IV
Frequent blood
glucose
monitoring
Caution: ALWAYS check with Regional Poison
Control Center for definitive treatment.
Anticholinergic toxidrome
Common with this toxidrome is the mnemonic
“blind as a bat, mad as a hatter, red as a beet,
dry as a bone, and hot as Hades or a hare.”
Common drugs that cause this toxidrome are
antihistamines, TCAs, and ingestion of Atropa
belladonna, antipsychotic antidepressants,
Skeletal Muscle Relaxants (SMRs), jimson
weed,
amantadine,
parasympatholytic
medications,
atropine,
scopolamine,
hyoscyamine, Amanita muscaria mushrooms,
and antiparkinson medication (Kemmerer,
881
2007). Treatment is focused on managing
symptoms such as decreasing fever and
agitation. Anticholinergic toxicity is caused by
agents that antagonize acetylcholine at
peripheral muscarinic and central receptors.
This causes inhibition at muscarinic receptors,
which leads to symptoms of anticholinergic
toxicity. Symptoms include hot flushes, dry
skin, dilated pupils, rapid heart rates, agitation,
confusion, anxiety, psychosis, constipation,
urinary retention, and ileus. Symptoms can be
delayed due to the effects on the gastric motility
of this class of drugs and effects are often
prolonged over 2–3 days. Diagnosis is based on
the history of ingestion. Overdose requires
monitoring in a critical care unit due to the
extreme agitation and tachycardia. Treatment is
supportive with IV crystalloids, continuous ECG
monitoring, electrolytes, CBC, CPK, and ABG
monitoring. Hyperthermia and rhabdomyolysis
can occur and cooling and aggressive fluid
management may be needed to prevent organ
damage and acute kidney injury. Seizures and
cardiac arrest can occur with tricyclic overdose
and antihistamines. In extreme and severe
toxicity such as hyperthermia, tachycardia, and
delirium, a small dose of physostigmine 0.5–1
mg IV can be given. Physostigmine can cause
AV blocks, asystole, and seizures, especially in
tricyclic overdose (Reilly and Stawicki, 2008).
Medications that should be avoided with this
toxidrome include haloperidol, phenytoin, and
882
Class IA, C, and
(Kemmerer, 2007).
III
antiarrhythmics
Benzodiazepine toxidrome
Respiratory depression and altered mental
status are common symptoms seen with this
type of overdose. Vital signs are usually stable
but hypotension can occur. Common drugs
include Xanax, Ativan, and Klonopin. Altered
mental status and coma are common and can
range from mildly lethargic to deep coma states
that require intubation to protect airway.
Flumazenil can be used in acute benzodiazepine
overdose. Dosages are 0.2 mg IVP with
additional doses up to 1 mg given at 1 min
intervals. Total dose should not exceed 3 mg/h.
Cholinergic toxidrome
This toxidrome is seen with drugs that directly
stimulate cholinergic receptors or inhibit
acetylcholinesterase. Remember the mnemonic
“SLUDGE” (salivation, lacrimation, urination,
defecation, gastric emesis) (Reilly and Stawicki,
2008). Symptoms vary depending on whether
stimulation is at the muscarine, nicotinic, or
central cholinergic receptor. Other symptoms
include bradycardia, bronchospasm, seizures,
and death. The most common drugs that cause
signs and symptoms of cholinergic toxicity are
organophosphates and certain mushrooms.
Neostigmine, which is a drug that can be given
to stimulate bowel function, can also cause
883
these effects. The treatment of this toxidrome is
usually supportive. The drug antidote is
atropine, which reverses the muscarinic effects
in organophosphate poisoning or the use of
nerve gas agents. The dose of atropine is 2–6
mg IVP and can be escalated every 3–5 min
until bronchospasm or wheezing stops.
Atropine infusion may be needed for continuing
symptoms. The hourly infusion rate is set at
20–30% of the total amount of atropine that is
required to stabilize the patient. The infusion is
maintained for 2–3 days with daily dose
reductions of 25–33% (Reilly and Stawicki,
2008). Pralidoxime therapy may also be used in
patients with signs and symptoms of
organophosphate poisoning. It is specifically
recommended for poisoning with carbamate.
Pralidoxime reactivates cholinesterase after
poisoning with an anticholinesterase agent. The
recommended dose is 1–2 g IV over 30 min
followed by a continuous infusion at 8 mg/kg/h
in adults. This drug is especially useful for
organophosphate poisoning that causes muscle
paralysis.
Opioid toxidrome
These drugs bind to opioid receptors and cause
CNS depression, bradycardia, hypotension,
pinpoint pupils, decreased gastric motility, and
constipation. Hypothermia is also common.
Narcan can be given for reversal. Clonidine
overdose can sometimes be confused with
884
opioid overdose because clonidine is an alpha 2
adrenergic
agonist
that
causes
G
protein-mediated potassium efflux like Mu
receptors, which cause hyperpolarization of
neurons in the CNS. Both alpha agonists and
Mu agonists cause pinpoint pupils, respiratory
depression, and coma. Narcan can be given but
the effect is not reliable in clonidine overdose.
Sympathomimetic toxidromes
This toxidrome is generally seen from an
overdose of stimulant drugs. Signs and
symptoms include diaphoresis, psychomotor
agitation, hallucinations, dilated pupils, tremor,
seizures,
dysrhythmias,
hypotension,
hyperthermia (especially with MDMA, PCP,
bath
salts,
and
hallucinogens),
fever,
tachycardia, diaphoresis, and hypertension.
Common drugs are theophylline, OTC
decongestants,
crack
cocaine,
cocaine,
amphetamines,
LSD,
nicotine,
ecstasy
(MDMA), caffeine, PCP, and MAOI. Other
drugs have sympathomimetic activity such as
clonidine, certain decongestants, and herbals.
This syndrome results from the release of or
blocking of the reuptake of dopamine and
norepinephrine, resulting in central and
peripheral adrenergic hyperactivity from
catecholamine
release.
Some
sympathomimetics can also inhibit serotonin
reuptake and norepinephrine (called SNRIs),
which may cause adverse effects of
885
hallucinations and extreme confusion with
overdose or withdrawal. Examples of these
drugs are Cymbalta, Effexor, and Pristiq. Drugs
that have pure alpha or beta activity will
produce varying symptoms.
Common
cardiovascular
symptoms
are
tachycardia, hypertension, tachypnea, and
hyperthermia. Common neurological symptoms
include agitation, psychomotor agitation,
hyperreflexia, and seizures. Other effects
include rhabdomyolysis, acute lung injury, and
vasospasm of arteries with organ injury.
Confusion can exist between this syndrome and
anticholinergic poisoning. The main difference
is the absence of diaphoresis in anticholinergic
poisoning.
Management is supportive and geared toward
treatment of the symptoms associated with this
toxidrome. Large doses of benzodiazepines are
needed to treat the neurological symptoms of
muscular
rigidity
and
cardiovascular
stimulation. Cardioversion or adenosine is
usually ineffective to treat supraventricular
tachycardias resulting from sympathomimetic
overdose. Beta blockers are more effective
(Givens and O’Connell, 2007). Crystalloid fluid
resuscitation and active cooling measures may
be needed.
886
Rhabdomyolysis syndromes
Rhabdomyolysis is a clinical condition that is
caused by leakage of intracellular myocytes
from muscle damage injury. This injury causes
excessive myoglobin to be released and
ferrihemate and globulin to form at pH levels of
5.6. Ferrihemate causes a deterioration of
kidney function by impairing renal tubular
transport mechanisms and leads to tubular
obstruction and cell death (Coco and Klasner,
2004). These injuries can be caused by drugs,
alcohol, local muscle compression in coma,
excessive muscular hyperactivity, rigidity, and
seizures. Common drugs associated with
elevated CPK levels and resulting in
rhabdomyolysis are amphetamines and their
derivatives, cocaine, clozapine, Zyprexa,
lithium, MAOIs, phencyclidine, strychine,
tetanus, and TCAs. Rhabdomyolysis from direct
cellular
toxicity
can
be
caused
by
amatoxin-containing
mushrooms,
CO,
colchicines, and ethylene glycol. Unknown
mechanisms causing elevated CPK levels
include barbiturates, chlorophenoxy herbicides,
ethanol, gemfibrozil, hemlock, hyperthermia,
statins, and trauma. Signs and symptoms
include very high CPK levels, myalgias, swelling
or tenderness over effected muscles signifying
developing
compartment
syndrome
hyperkalemia, hyponatremia, hypocalcemia,
and decreased phosphorous levels.
887
Strychnine can also cause rhabdomyolysis; it
has an alkaloid base, which can be found in
rodent poison. It can also be found as an
additive to cocaine or heroin. Strychnine causes
increased neuronal rigidity, which can result
generalized seizure activity and contraction of
skeletal muscles. These muscle spasms may
produce rhabdomyolosis, fever, or respiratory
paralysis. Diagnosis is usually based on a
history of ingestion. Specific levels can be
measured in urine, blood, and bile, but
generally may not be useful for toxic symptoms
due to lack of correlation with levels. Treatment
is supportive by maintaining airway. Symptoms
of strychnine poisoning usually abate within
several hours. Muscular rigidity is treated with
benzodiazapines. Charcoal can be given within
a couple of hours of ingestion of involved
substances. Paralytic agents may be needed for
severe muscle spasm and contraction. If
compartment syndrome develops, surgical
fasciotomy may be needed. Treatment with
crystalloid fluids at rates of 200–300 cc/h to
maintain urine output at 100 cc/h or greater is
essential to prevent acute tubular necrosis.
Treatment with mannitol and bicarbonate to
increase urinary pH has shown to be effective in
some patients with acute tubular necrosis but
use of bicarbonate may potentiate an existing
hypocalcemia (Coco and Klasner, 2004).
888
Treatment of hyperkalemia
The common treatment for hyperkalemia
consists of giving 1– 2 amps (50–100 mEq) of
sodium bicarbonate, 1 amp of calcium chloride
IV, and 1 amp of D50 with 10 units of regular
insulin IV. If the patient is able to take
medications by mouth or has an intact GI
system, Kayexalate can be given either by
mouth, nasogastric tube, or rectally in doses of
15–30 g 1–4 times daily or until bowel
movement occurs. The rectal dose is 30–50 g
given as a retention enema every 6 h until
stooling or resolution of hyperkalemia.
Remember! Common arrhythmias are peaked
T waves, but hyperkalemia alters the QRS
complex, leading to bradycardia and AV blocks
with later effects of hyperkalemia. These may
respond
to
dopamine
infusion
and
transcutanous pacing followed by transvenous
pacing and acute dialysis. Isuprel has also been
used. These treatments should be followed by
urgent hemodialysis.
Packidrome
Packidrome is the unofficial term that describes
mixed toxidromes. Body packers is a term
applied to people who intentionally swallow
packets of drugs that can contain cocaine or
heroin. These packets can leak or burst and
cause extreme toxicity. Abdominal X-rays and
CT scanning can be useful but may miss
889
packages. Decontamination with charcoal can
be useful and polyethylene glycol electrolyte
lavage solution (PEG-ELS) has been used to
decrease transit time. Emergent surgery with
need for enterotomy may be required in case of
packet rupture.
Alcohol withdrawal syndrome
Withdrawal
from
alcohol
produces
a
hyperadrenergic state that is manifested by
hyperexcitability,
tremors,
hallucinations,
confusion, tachycardia, hypertension, and
agitation. Tremors indicate mild to moderate
withdrawal and generally occur within 6–8 h
after last ethanol ingestion. Most seizures
associated with alcohol withdrawal occur within
48–72 h of last ingested ethanol. Status
epilecticus is a rare occurrence. The most severe
form of ethanol withdrawal is called delirium
tremens. This is usually seen within the first
48–72 h but may be delayed in some cases for
up to 14 days. The main symptoms of delirium
tremens involve a series of life-threatening
autonomic hypersensitivity. Symptoms include
extreme agitation, confusion, hallucinations
both visual and auditory, garbled speech,
tachycardia,
hypertension,
hyperpyrexia,
diaphoresis, and mydriasis. Generally, ethanol
withdrawal lasts from 1 to 6 days and generally
peaks at 5 days. Alcohol withdrawal can persist
past 5 days.
890
Treatment usually involves protocols that are
hospital-specific and involves assessment tools
to grade the severity of withdrawal syndrome
and to treat the symptoms. A common scale
used is the Clinical Institute Withdrawal
Assessment (CIWA), which is based on a
grading and scoring system according to which
medication doses are administered (Spiegel,
Kumari, and Petri, 2012). Generally, treatment
is with a short- or long-acting form of
benzodiazepine. Antipsychotics may be used
such as Haldol, Zyprexa, or Seraquel but
caution should be used not to induce seizures.
Monitoring of the QTc interval should also be
done at initiation and during dosing. An
antihypertensive may also be ordered such as
metropolol or clonidine for autonomic
dysfunction and cardiovascular strain from
alcohol withdrawal symptoms.
Clinical Pearls
Caution should be used with lorazepam
infusion as the active metabolite contained in
the IV form can cause an anion gap acidosis
that is attributed to PG toxicity. Midazolam
infusion is commonly used with monitoring
of infusion generally done in critical care
units due to risk of respiratory depression.
End-tidal CO2 should also be monitored.
891
Anion and non-anion gap
acidosis and osmolar anion gap
Certain acidotic states can help the practitioner
diagnose what may have been ingested. If an
anion gap acidosis is present, an osmolar gap
should be measured. The definition of anion
gap is the difference between measured cations
and anions. In an increased anion gap
metabolic acidosis, an anion that is not
measured in the electrolyte panel accumulates
in the blood. Serum bicarbonate levels decrease
as it is consumed during neutralization of this
compound or acid, therefore increasing the
calculated anion gap. Some causes of elevated
anion gap are included in the mnemonic
“MUDPILES”:
M—methanol, metformin
U—uremia (renal failure), hepatorenal failure
D—diabetic ketoacidosis
P—paraldehyde, propofol, propylene glycol
I—iron, isoniazid, ibuprofen
L—lactic acidosis, which could also be
conditions leading to lactic acidosis such as
seizure, hyperthermia, hypotension, low
perfusion states, carbon monoxide, and
hydrogen sulfate
E—ethylene glycol, ethanol
892
S—salicylates, starvation ketoacidosis (adapted
from Levine et al., 2011, p. 799)
Additional substances that may produce mild
anion gap include theophylline. Toluene (from
glue sniffing) use also produces non-anion gap
acidosis.
The calculation is as follows: [serum sodium] –
[serum chloride + serum bicarbonate] = anion
gap
The normal anion gap is less than 16 mEq/l.
Some causes of decreased anion gap are
hypoalbuminemia, congestive heart failure,
multiple myeloma, lithium, iodine toxicity, and
administration of aminoglycosides. There are
many online calculators that can help you
calculate this number.
Non-anion gap acidosis
This can also be called normal anion gap
acidosis. It develops from an increased
excretion of bicarbonate or increased
production of chloride (e.g., hyperchloremic
acidosis from excessive normal saline infusion).
It presents as an acidosis that is not
accompanied by an anion gap. It can easily be
remembered by the mnemonic “HARD-UP.”
Some causes are
hyperalimintation,
acetazolamide,
893
renal tubular acidosis,
diarrhea, or a
ureteroenteric or
pancreaticoduodenal fistula.
Osmolar gap
Osmolality is the measurement of the number
of particles dissolved in a kilogram of solvent.
Osmolarity is the actual number of particles per
liter of solution. An elevated osmolar gap
suggests that there is an unmeasured solute
(Levine et al., 2011). Major osmotically active
solutes are sodium, glucose, bicarbonate, urea,
chloride, and potassium. These are measured in
the calculated osmolarity equation:
Normal osmolarity is 280–295
To calculate osmolar gap (which is the
difference between the measured serum
osmolarity and the calculated result), check a
serum osmolarity level, calculate the serum
osmolarity, then subtract that number from the
other to get the osmolar gap. Osmolar gap also
needs to be corrected in the setting of a positive
ETOH level. To correct for ETOH, take the
ETOH level, divide by 4, and add that number
to the calculated osmolarity, then subtract this
894
number from the measured osmolarity. For
example, the equation would look like this:
Osmolarity corrected for elevated ETOH
level
The calculated osmolarity is then subtracted
from the measured serum osmolarity to identify
the osmolar gap. The normal osmolar gap is
less than 10 mEq/l.
Drug ingestions that cause an increased
osmolar gap include ethanol, methanol,
isopropyl alcohol, ethylene glycol, and
propylene glycol. Nontoxic causes include DKA,
renal failure, severe hyperlipidemia, inaccurate
testing techniques, mannitol, and glycerol. If an
osmolar gap is present without an anion gap,
common causes may include isopropyl alcohol
ingestion, sickle cell syndrome in multisystem
organ failure, absorption of sorbital, and
intravenous immunoglobulin (IVIG) infusions.
The monitoring and treatment of drug and
substance overdoses is complex and continually
changing. This chapter has covered many
common overdoses resulting in ICU admissions
but continual research is needed for most
categories of treatment and conditions.
Regional Poison Control Centers are an
excellent resource to support strong clinical
895
history and physical assessment skills. Because
overdoses may be accidental or intentional,
strong patient advocacy and social assessments
are paramount in determining type and
progression of overdose symptoms as well as
meaningful support for those affected by the
overdose.
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912
Index
abdominal trauma
abdominal compartment syndrome
organ dysfunction and intracompartmental
pressure
stages of damage control surgery
absolute neutrophil count (ANC) calculation
acetaminophen
antidotes/binding agents
diagnostic testing and monitoring
drug overview
symptoms of overdose
acid-base disturbances
activated protein C (APC)
acute care advanced practice nursing
acute care nurse practitioners (ACNP)
outcomes research
acute coronary syndrome
evidence-based treatment guidelines
monitoring elements
use of alarms
913
acute heart failure
cardiogenic dyspnea in
monitoring elements
acute interstitial nephritis (AIN)
drugs causing
acute kidney injury (AKI)
causes
classification
diagnostic imaging
electrolye imbalances
evidence-based treatment guidelines
hemodynamic monitoring
management of electrolye and acid-base
imbalance
pharmacologic interventions
prevention of radiocontrast nephropathy
volume expansion
incidence
intrarenal (intrinsic) injury
mortality rate
physiological guidelines
post renal injury
history and physical assessment
914
laboratory analysis and data trending
monitoring elements
nutrition
prerenal injury
prevention
renal biopsy
renal replacement therapy (RRT)
RIFLE classification
traditional oncologic emergencies
urinary findings
acute liver failure (ALF)
acute lymphoblastic leukemia (ALL)
acute myeloid leukemia
acute respiratory failure
hypercapnic
hypoxemic
inability to maintain airway
acute tubular necrosis (ATN)
acute variceal hemorrhage
adult respiratory distress syndrome (ARDS)
advanced directives
advanced practice registered nurses (APRNs)
air tonometry
915
aiway pressure release ventilation (APRV)
alarms
alcohol withdrawal syndrome
allopurinol
alveolar hemorrhage (DAH)
Ambu bag-valve mask
American Association of Critical Care Nurses
(AACN)
American Nurses Certification Corporation
(ANCC)
amphetamines
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
anaphylactic shock
algorithm
aneroid blood pressure measurement
angiosarcoma
angiotensin-converting enzyme (ACE)
inhibitors
angiotensin receptor blockers (ARB)
anion gap acidosis
anion gap metabolic acidosis
916
antiarrhythmic agents
overdose
antibiotics
in burns
in neutropenia
in open fractures
anticholinergic toxidrome
anticholinergics/cholinergics/antihistamines
(ACA)
antidotes/binding agents/treatment
diagnostic testing and monitoring
drug overview
symptoms of overdose
anticonvulsants
antidotes/binding agents
diagnostic testing and monitoring
drug overview
symptoms of overdose
antithymocyte globulin
aplastic anemia
apnea
apnea–hypopnea index
ARDS Network
917
ARDSNet protocol goals
argon-plasma electrocoagulation
arrhythmias, cardiac
ECG monitoring classifications
evidence-based treatment guidelines
monitoring elements
unnecessary monitoring
arterial blood gas (ABG) analysis
arterial oxygen saturation
arterial pressure (AP)
arteriovenous oxygen content difference
(C[a−v]O2)
Aspergillus
assist/control ventilation (AC)
asthma
waveform in
asystole
atrial fibrillation (AF)
atrial septal closure devices
AV block
bacitracin
bad news, delivering
balloon bronchoplasty
918
balloon tamponade therapy
barbituates
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
bath salts
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose/use
benzodiazepine toxidrome
benzodiazepines
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
best practice
beta blockers
antidotes/binding agents/treatment
diagnostic testing and monitoring
overdose: effects and treatment
symptoms of overdose
919
beta-lactams
bilevel positive airway pressure (BiPAP)
in sleep disorders
bioartificial liver support (BAL)
BiSpectral index (BIS)
evidence-based treatment guidelines
monitoring elements
blood pressure monitoring
aneroid
arterial pressure
cuff sizes
noninvasive
oscillometric
brachytherapy
bradycardias
bradypnea
BRAIN card
brain, traumatic injury management algorithm
brain temperature measurement
evidence-based treatment guidelines
brain vs body temperatures
brain tissue oxygen monitoring
monitoring elements
920
evidence-based treatment guidelines
bronchiolitis obliterans
bronchoscopy
Burkitt’s lymphoma
burns
classification
depth
evaluation
Lund/Browder chart
fluid management
antibiotics in
Burns Wean Assessment Program (BWAP)
busulfan
C-reactive protein (CRP)
calcium channel blockers (CCBs)
antidotes/binding agents/treatment
diagnostic testing and monitoring
pharmacology
symptoms of overdose
candidiasis
capnography
monitoring blood flow
monitoring ventilation with PetCO2
921
phases
capnometry
carbapenem
carbon monoxide
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
pharmacology
symptoms
cardiac arrest, recognition of
Cardiac Index (CI)
cardiac medications
cardiac output (CO)
cardiac tamponade
management
monitoring
physiologic guidelines
cardiogenic dyspnea
cardiogenic shock
causes
frequency
cardiopulmonary bypass as cause of acute
kidney injury
922
cardiovascular disease, ECG in
evidence-based treatment guidelines
goals of monitoring
incidence
monitoring elements
mortality rates
physiologic guidelines
post cardiopulmonary resuscitation
carotid blowout syndrome
algorithm
management
monitoring
physiologic guidelines
catheter-associated UTI (CAUTI)
cefipime
ceftazidime
central neurogenic hyperventilation
central sleep apnea (CSA)
central venous catheters (CVCs)
central venous pressure (CVP)
arterial line monitoring and management
monitoring and management
trending limitations
923
cerebral autoregulation
cerebral blood flow
increased intracranial pressure and
cerebral edema
cerebral fat embolism
cerebral perfusion pressure (CPP).
cerebral regulation
certification in CCUs
cervical stabilization devices
evidence-based treatment guidelines
monitoring elements
charcoal, activated, in drug overdose
chest radiograph interpretation
ARDS
pleural effusion
pneumothorax
white out areas
infiltrates
chest tube thoracotomy
Cheyne-Stokes breathing
cholinergic toxidrome
chronic low cardiac output states
chronic obstructive pulmonary disease (COPD)
924
cilastin
cirrhosis
clinical nurse specialists (CNSs)
Clostridium difficile
club drugs/date rape drugs, overdose
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
cocaine
antidotes/binding agents/treatment
diagnostic testing and monitoring
drug overview
symptoms of overdose
colonoscopy
coma, induced and sedation protocols
evidence-based treatment guidelines
monitoring elements
compartment syndrome, abdominal
as cause of acute kidney injury (AKI)
competency in CCUs
continuous arteriovenous hemodialfiltration
(CAVHDF)
925
continuous arteriovenous hemofiltration
(CAVH)
continuous cardiac output (CCO) monitoring
continuous positive airway pressure (CPAP)
in sleep disorders
continuous renal replacement therapies (CRRT)
continuous venovenous hemodialysis (CVVHD)
continuous venovenous hemofiltration (CWH)
continuous venvenous diafiltration (CVVHDF)
contrast-induced nephropathy (CIN)
coronary artery bypass graft (CABG)
cost of critical care
critical care delivery, organization of
critical care team
critical illnesses, ECG monitoring
evidence-based treatment guidelines
monitoring elements
Cushing’s response (Cushing’s reflex)
Cushing’s triad
cyclophosphamide
cyclosporine
cystatin C
cytomegalovirus (CMV)
926
daclizumab
dantrolene
in malignant hyperthermia
date rape drugs, overdose
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
deep vein thrombosis (DVT)
Defibrotide
dextromethorphan
antidotes
diagnostic testing and monitoring
drug overview
symptoms of overdose
diabetes
carbohydrate administration
critical care insulin infusion protocol
effects of hyperglycemia
fingerstick glucose (FSG) testing
glucose monitoring
hyperglycemia management
recommendations
927
hypoglycemia management
hypoglycemia protocol, mental status
insulin therapy
sleep disorders and
subcutaneous insulin correction scales for
tube-feeding diets
diabetic ketoacidosis (DKA)
diabetic nephropathy
antidotes/binding agents/treatment
diagnostic testing and monitoring
pharmacology/symptoms of overdose
digoxin toxicity
direct fluorescent antibody staining
disopyramide
disseminated intravascular coagulation (DIC)
dobutamine
dofetilide
drugs of abuse
diagnostic testing
overview
symptoms of overdose
see also under names
dysrhythmia monitoring
928
early goal-directed therapy (EGDT)
Eculizumab
electrocardiography (ECG)
electroencephalography (EEG) monitoring
electrolyte abnormalities
evidence-based treatment guidelines
management, in malignancy
monitoring elements
electrophysiological monitoring
evidence-based treatment guidelines
monitoring elements
emboli
endocarditis
end-of-life concerns
advanced directives
assessment and communication issues
brain death
delivering bad news
family presence
pain assessment
palliative care
palliative care in the ICU
SPIKES model
929
surrogate decision making
symptom management
endoscopic procedures
evidence-based treatment guidelines
intra- and postendoscopic therapy
stress ulcers
endoscopic variceal ligation (EVL)
end-stage liver disease (ESLD)
erythromycin
Escherichia coli
esophagogastric varices
esophagogastroduodenoscopy (EGD)
ethylene glycol
antidotes/binding agents/treatment
diagnostic testing and monitoring
symptoms of overdose
ETOH level
eupnea
expiratory positive airway pressure (EPAP)
extended daily dialysis (EDD)
external beam radiation therapy (EBRT)
extravascular lung water (EVLW)
fake marijuana
930
antidote
diagnostic testing
drug overview
symptoms
families
in critical care unit
end-of-life concerns and
febuxostat
fever in neutropenia
antibiotic treatment
persistent fever
fibrinolytic therapy and PCI
finger cuff blood pressure technology
finger stick glucose testing
FloTrac transducer
fluid management in burn therapy
fluid resuscitation
end points of resuscitation
fluid choice
massive transfusion product shipment
flumazenil (Romazicon)
folate deficiency
frequency of vital sign monitoring
931
fulminant hepatic failure
fundus paraproteinaemicus
furosemide
gastric lavage
gastric pH
evidence-based (SIGN) treatment guidelines
gastric tonometry
gastrointestinal system (GI)
bleeding, tests for
capnometry
clinical grades of hepatic encephalopathy
endoscopic procedures
evidence-based treatment guidelines
intra- and postendoscopic therapy
stress ulcers
(already listed, above)
gastrointestinal bleeding
gastrointestinal dysfunction
nasogastric decompression
radiographic diagnostics
ultrasonography
evidence-based treatment guidelines
FAST guidelines
932
intraabdominal pressure management
gemtuzumab
Glasgow Coma Scale
global end-diastolic volume (GEDV)
graft-versus-host disease
hallucinogens
drug overview
monitoring and treatment
symptoms of overdose
head tilt and chin lift
head-of-bed (HOB) elevation
heart blocks
heart rate monitoring
heatstroke
Helicobacter pylori
hematologic complications in malignancy
hemodynamic monitoring
overview
guidelines and outcomes
functional indicators
passive leg raising (PLR)
perioperative optimization
pulse contour analysis
933
SVV protocols for management
transesophageal monitoring
transpulmonary dilution techniques
volume responsiveness
principles
systems
terminology
hemolytic uremic syndrome (HUS)
hemopneumothorax
hemorrhagic complications in malignancy
Henderson–Hasselbach equation
hepatic encephalopathy
hepatic veno-occlusive disease
hepatitis
hepatorenal syndrome
high-dose insulin/glucose euglycemia (HIE)
therapy
Hopkins Model
hospital-associated pneumonia (HAP)
hydrocarbons and toxic inhalants
antidotes/treatment
diagnostic testing and monitoring
drug overview
934
pharmacology
signs and symptoms
hydrocephalus
hyperglycemia
carbohydrate administration
glucose monitoring
insulin therapy
management
hyperkalemia
treatment of
hyperleukocytosis
management
monitoring elements
physiologic guidelines
hyperphosphatemia
with secondary hypocalcemia
hyperpnea
hyperthermia
malignant (MH)
in sepsis
hyperuricemia
hyperviscosity syndromes
management
935
monitoring elements
physiologic guidelines
hypocalcemia
hypoglycemia
protocol, mental status
hypomagnesemia
hyponatremia
hypopnea
hypothermia
beneficial effects
complications
in sepsis
hypovolemic shock
hypoxia, restlessness in
ibutilide
idiopathic pneumonia syndrome (IPS)
imipenem
immune thrombocytopenia purpura (ITP)
implantable cardioverter defibrillator (ICD)
infliximab
influenza A and B
infrared absorption spectrophotometry
inspiratory positive airway pressure (IPAP)
936
insulin
critical care infusion protocol
in drug overdose
subcutaneous correction scales for
tube-feeding diets
intensive care unit (ICU) care systems
interleukin (IL)-18 in acute kidney injury
intermittent hemodialysis (IHD)
intraaortic balloon pump (IABP)
intracerebral hemorrhage (ICH)
intracranial hemorrhage
intracranial pressure, increased
cerebral response to
intracranial pressure monitoring
evidence-based treatment guidelines
monitoring elements
intrathoracic blood volume (ITBV)
intravenous lipid emulsion (ILE) therapy in
drug overdose
inverse ratio ventilation
Iowa Model
iron, overdose
antidotes/binding agents/treatment
diagnostic testing and monitoring
937
drug overview
symptoms of overdose
ischaemia, underutilization of
isopropyl alcohol drugs
antidotes/binding agents/treatment
diagnostic testing and monitoring
symptoms of overdose
IV immune globulin
jaw thrust
jugular venous saturation (SjO2)
ketamine
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
ketorolac (Toradol) in orthopedic injury
kidney injury molecule-1 (KIM-1) in acute
kidney injury
Klebsiella pneumonia
knowledge transformation processes
Kussmaul breathing
lactic acidosis
938
left ventricular end-diastolic pressure (LVEDP)
left ventricular stroke work index (LVSWI)
Legionella species
leukemia
acute lymphoblastic
acute myeloid
lymphoid
leukostasis
management
monitoring elements
physiologic guidelines
level of consciousness (LOC)
ligament of Treitz
lithium
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptom of overdose
liver biopsy
liver failure, acute, ICP monitoring in
ascites management
evidence-based treatment guidelines:
paracentesis
939
evidenced-based treatment guidelines
nutritional assessment and treatment
liver function diagnostics
liver support devices
evidence-based treatment guidelines
local anesthetic systemic toxicity (LAST)
long QT syndrome
Lund/Browder chart
lymphoblastic lymphomas
lymphoma
Burkitt’s
lymphoblastic
non-Hodgkins
malignant airway obstruction
management
monitoring
physiologic guidelines
malignant fibrous histiocytoma
malignant hyperthermia (MH)
clinical signs
mechanical ventilation
auto-PEEP effect
complications
940
high peak airway pressures
modes of
response to bagging
weaning from
melphalan
meningitis
meropenem
metabolic acidosis
causes
diagnostic algorithm
due to acute kidney injury
metabolic alkalosis
diagnostic algorithm
metacloprimide
methanol overdose
antidotes/binding agents/treatment
diagnostic testing and monitoring
symptoms of overdose
methemyoglobin
antidotes/binding agents/treatment
diagnostic testing and monitoring
drug overview
symptoms of overdose
941
methotrexate
microdialysis
evidence-based treatment guidelines
monitoring elements
milrinone
mixed acid-base disorders
mixed central venous saturation (ScvO2)
mixed venous oxygen saturation (SvO2)
factors affecting
monoamine oxidase inhibitors
antidotes
diagnostic testing and monitoring
drug overview
MAO/MAOI food interactions
symptoms of overdose
Monroe–Kellie hypothesis
multiple myeloma
multisystem organ dysfunction syndrome
(MODS)
musculoskeletal injury
compartment syndrome
crush syndrome management
extremity nerve assessment
942
nerve injury
ongoing hemorrhage
pain management in orthopedic injury
pelvic fractures
prophylactic antibiotic use in open fractures
Mycobacterium
mycophenolate mofetil
myelodysplastic syndrome
myocardial infarction (MI)
biomarkers
myxedema
N-acetylcysteine (NAC)
naloxone
nasal pillows
nasogastric decompression
National Association of Clinical Nurse
Specialists (NACNS)
National Clearinghouse Guidelines Index
guidelines
National Institute of Health Stroke Scale
(NIHSS)
necrotizing entercolitis
needle thoracostomy
943
neodynium:yttrium aluminum garnet
(Nd:YAG) laser
neuroleptics
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
neurologic dysfunction
evidence-based treatment guidelines
monitoring elements
pupillary dysfunction
rapid assessment
neuromuscular transmission
evidence-based treatment guidelines
monitoring elements
neutropenia management
assessment and monitoring in
evidence-based guidelines
persistent fever
neutrophil gelatinase–associated lipocalin
(NGAL) in acute kidney injury
nitrates
antidotes/binding agents/treatment
diagnostic testing and monitoring
944
pharmacology
symptoms of overdose
non-anion gap acidosis
non-Hodgkin’s lymphoma
noninvasive blood pressure (NIBP)
measurement
noninvasive positive pressure ventilation
(NIPPV)
nonsteroidal anti-inflammatory drugs
(NSAIDs)
antidotes/binding agents/treatment
drug overview
monitoring
in orthopedic injury
symptoms of overdose
Numerical Rating Scale
nursing certification in CCUs
obesity, CVD and
obesity hypoventilation syndrome (OHS).
obstruction, as cause of acute kidney injury
(AKI)
obstructive sleep apnea (OSA)
obstructive sleep apnea–hypopnea syndrome
(OSAHS)
945
octreotide for sulfonylurea overdose
opioid toxidrome
opioids
antidotes/binding agents/treatment
diagnostic testing and monitoring
drug overview
symptoms of overdose
oscillatory ventilation
oscillometric blood pressure measurement
osmolar gap
osteomyelitis
overdoses
drug-induced hyperthermia syndromes
drug screening
general management
history taking
indexing of drug and toxins
law enforcement
new and emerging therapies
overwhelming post-splenectomy sepsis (OPSS)
oxygen consumption
oxygen delivery (DO2)
oxygenation
946
acute respiratory failure
alveolar-arterial oxygen (A-a) gradient
estimation of PaO2
PaO2/FiO2 (P/F) ratio
ozogamicin
pacemaker
Packidrome
palliative care in the ICU
brain death
pancreatitis
acute
partial pressure brain tissue oxygen (PbtO2)
passive leg raising (PLR)
pelvic fractures
peptic ulcer
percutaneous coronary intervention (PCI)
pericarditis
peritoneal dialysis (PD)
continuous renal replacement therapies
peritonitis
permissive hypercapnia
phencyclidine
antidotes/binding agents/treatments
947
diagnostic testing and monitoring
drug overview
symptoms of overdose
phenothiazines overdose
piperacillin
plethysmography analysis
pleural effusion
Pneumocystis jiroveci (pneumocystis
pneumonia (PCP)
pneumocystis pneumonia (PCP)
pneumothorax
positive end expiratory pressure (PEEP)
titration
postextubation stridor
potassium blockers
antidotes/binding agents/treatment
diagnostic testing and monitoring
pharmacology
symptoms of overdose
premature ventricular contractions (PVCs)
pressure control ventilation
pressure-regulated volume control (PRVC)
Prinzmetal angina
procainamide
948
Procalcitonin (PCT)
propylene glycol
antidotes/binding agents/treatment
diagnostic testing and monitoring
symptoms of overdose
proton pump inhibitors (PPIs)
Pseudomonas aeruginosa
psychiatric drugs
pulmonary artery catheter monitoring
pulmonary artery occlusive pressure (PAOP)
pulmonary artery pressure (PAP)
pulmonary embolus
pulmonary fibrosis
pulmonary infections
pulse contour analysis
pulse contour cardiac output (PiCCO) system
PiCCOR
pulse oximetry
waveforms (Δ POP)
pulse pressure (PP)
pupillometer
QT-interval monitoring
underutilization of
949
QT interval, prolonged, drugs causing
QTc measurement
Quality and Safety Education for Nurses
(QSEN)
quinidine
rapid response team (RRT)
rasburicase
renal acidosis
renal dysfunction
renal replacement therapy (RRT)
comparison
continuous renal replacement therapies
intermittent hemodialysis (IHD)
peritoneal dialysis
respiratory acidosis
diagnostic algorithm
respiratory alkalosis
compensatory mechanisms
diagnostic algorithm
overventilation
Respiratory Distress Observation Scale (RDOS)
respiratory monitoring
respiratory patterns
950
abnormal
return of spontaneous circulation (ROSC)
rhabdomyolysis
rhabdomyosarcoma
rheumatoid arthritis
rib fractures
RIFLE criteria
right atrial pressure (RAP)
right ventricular stroke work index
rituximab
Rule of Nines
salicylates
antidotes/binding agents/treatment
drug overview
monitoring
symptoms of overdose
scleroderma
sedation protocols
seizure
selective serotonin reuptake inhibitors
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
951
symptoms
sepsis
assessment
blood cultures
body temperature
diagnostic criteria
early goal-directed therapy (EGDT) in
in immunocompromised host
intravascular catheters
risk factors
severe
sepsis syndromes
incidence
monitoring and treatment priorities in
see also sepsis
septic shock
serum-ascites albumin gradient (SAAG)
shock conditions
definition
shock index (SI)
shunts
evidence-based treatment guidelines
monitoring elements
952
sirolimus
skeletal muscle relaxants
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
sleep disorders
breathing
diabetes and
slow continuous ultrafiltration (SCUF)
Society of Critical Care Medicine
sodium channel blockers
antidotes/binding agents/treatment
diagnostic testing and monitoring
symptoms of overdose
sotalol
SPIKES model
spinal cord compression
sputum sampling
SPV
ST segment monitoring
Staphylococcus aureus
stem cell transplant
953
graft-versus-host disease
hepatic veno-occlusive disease (sinusoidal
obstructive syndrome (SOS))
infection
pulmonary complications
stoke, acute ischemic
STOP-BANG questionnaire
Streptococcus pneumoniae
stress-related mucosal disease
stroke
stroke volume (SV)
stroke volume index (SVI)
stroke volume variation (SVV)
fluid responsiveness and
mechanisms of, during positive pressure
ventilation
Stryker Intracompartmental Pressure Monitor
ST-segment elevated myocardial infarction
(STEMI)
ST-segment monitoring
subarachnoid hemorrhage
sucralfate
superior vena cava syndrome
surveillance
954
Surviving Sepsis Campaign, The
sustained low-efficiency dialysis (SLED)
sylvian arachnoid cysts
Sympathomimetic toxidromes
synchronized intermittent mandatory
ventilation (SIMV)
syncope
systemic inflammatory response syndrome
(SIRS)
systemic lupus erythematosus
tachycardias, wide and narrow complex
tachypnea
tacrolimus
tazobactam monotherapy
temperature, body
monitoring
in sepsis
tension pneumothorax
thoracentesis, diagnostic
thoracic injury management
thrombocytopenia
causes
chemotherapeutic treatments
955
management
monitoring elements
nonchemotherapeutic drugs
thrombotic microangiopathy (TMA)
ADAMTS13 deficiency
causes
management
monitoring elements
pathophysiology
physiologic guidelines
post-transplant
therapeutic plama exchange (TPE) in
thrombotic thrombocytopenia purpura (TTP)
torsades de pointes
total body surface area (TBSA)
total parenteral nutrition (TPN)
in abdominal trauma
toxic alcohols
toxidromes
Toxoplasma gondii
transcranial Doppler ultrasonography
evidence-based treatment guidelines
monitoring elements
956
transesophageal Doppler (TED)
transesophageal monitoring
transfer protocols
transjugular intrahepatic portosystemic shunts
(TIPS)
transport, monitoring during
transpulmonary dilution techniques
trauma
abdominal
anticoagulation
as cause of acute kidney injury (AKI)
complications
differential diagnosis
early mobilization
fluid resuscitation
gastrointestinal
intracompartmental monitoring
musculoskeletal
pain management
primary and secondary surveys
tertiary surveys
thromboembolic events
traumatic brain injury management
algorithm
957
thoracic injury management
see also burns
tricyclic antidepressant (TCA) overdose
antidotes/binding agents/treatments
diagnostic testing and monitoring
drug overview
symptoms of overdose
tuberculosis
tumor lysis syndrome
monitoring
physiologic guidelines
signs and symptoms
treatment
typhlitis
ulcers
peptic
stress
urinary antigen testing
urinary tract infections
ursodiol
US critical care units
US national critical care organizations
V/Q mismatch
958
valvuloplasty
vancomycin
vasopressin
venous oxygen content (CvO2)
ventilator-associated pneumonia (VAP)
ventricular arrhythmias, alarms and
ventricular fibrillation
ventricular tachycardia
nonsustained
ventriculostomy
vital signs monitoring
vitamin B12 deficiency
Waldenstrom macroglobulinemia (WM)
warfarin
WEANS NOW checklist
Wellen’s sign
Wolf–Parkinson White syndrome
959
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